Community signal

Discovery of a novel and potent KRAS(G12V)-targeting peptide with antiproliferative activity against colorectal cancer cells.

1. J Enzyme Inhib Med Chem. 2026 Dec;41(1):2684700. doi: 10.1080/14756366.2026.2684700. Epub 2026 Jun 11. Discovery of a novel and potent KRAS(G12V)-targeting peptide with antiproliferative activity against colorectal cancer cells. Zhang H(1), Yang S(2), Wang Y(2), Niu MM(2), She J(3). Author information: (1)Department of Hepatobiliary Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China. (2)Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, Jiangsu, China. (3)Department of Gastrointestinal Surgery, Jintan Affiliated Hospital of Jiangsu University, Changzhou, Jiangsu, China. Despite the clinical relevance of KRASG12V in colorectal cancer, KRASG12V-specific inhibitors remain limited. Through structure-based virtual screening of a 59,319-member peptide library, we identified four KRASG12V-targeting peptides, among which Peptide-1 showed the most favourable docking profile. MST assays confirmed Peptide-1 had the highest affinity among Peptides 1-4, with stronger binding to KRASG12V than to other KRAS mutants. Structural analysis, molecular dynamics simulations, and free-energy calculations indicated that Peptide-1 formed a stable and energetically favourable complex with KRASG12V through extensive hydrogen bonding and hydrophobic interactions. Peptide-1 showed favourable human serum stability and cellular NanoBRET-supported engagement with KRASG12V. Functionally, Peptide-1 displayed potent antiproliferative activity in colorectal cancer cell lines, weaker effects on normal cells and reduced efficacy after KRASG12V knockdown. In SW480 cells, Peptide-1 was associated with reduced ERK1/2 phosphorylation, p21 upregulation, and G0/G1 accumulation. Overall, these findings support further investigation of Peptide-1 as a KRASG12V-targeting peptide for colorectal cancer drug discovery. DOI: 10.1080/14756366.2026.2684700 PMCID: PMC13262105 PMID: 42274165 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the authors.

Mentions P21

AMD1-mediated polyamine metabolism governs tubular repair fate by restraining senescence after kidney injury.

1. Ren Fail. 2026 Dec;48(1):2680375. doi: 10.1080/0886022X.2026.2680375. Epub 2026 Jun 14. AMD1-mediated polyamine metabolism governs tubular repair fate by restraining senescence after kidney injury. Mao B(1)(2)(3), Zheng Z(1)(2)(3), Fu W(1)(2)(3), Cheng G(1)(2)(3), Wang L(1)(2), Bao J(1)(2), Liu X(4)(5), Zhan H(4)(5), Pan M(4)(5), Liu J(1)(2)(3). Author information: (1)Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (2)Laboratory of Nephropathy, Translational Medicine Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (3)Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (4)Department of Nephrology, Ningde Municipal Hospital of Ningde Normal University, Ningde, China. (5)Department of Nephrology, Shanghai First People's Hospital Ningde Hospital, Ningde, China. Failure of adaptive repair after acute kidney injury (AKI) drives the transition to chronic kidney disease (CKD), yet the metabolic checkpoints governing tubular fate remain incompletely defined. Here, we investigated whether the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase 1 (AMD1) regulates tubular senescence and repair outcomes after AKI and elucidated the underlying mechanism. AMD1 dynamics were examined in an ischemia-reperfusion injury model using male C57BL/6J mice by immunofluorescence. AAV-mediated Ksp promoter-driven tubule-specific Amd1 conditional knockdown male mice (Amd1 cKD) were used to assess renal injury, cell-cycle status, senescence, and remodeling, and exogenous spermidine was administered for rescue. DNA damage signaling and p53/p21 activation were evaluated by immunostaining, Western blotting, and EdU incorporation assays. AMD1 was predominantly expressed in the tubular epithelium, with prominent dynamic induction in proximal tubules early after IRI, but declined to baseline levels during the late phase, representing a relative metabolic insufficiency that correlated inversely with fibrosis. Compared with wild-type controls, Amd1 cKD mice exhibited aggravated tubular injury, an over two-fold increase in SA-β-gal-positive areas, elevated p21, and reduced Ki67+ proliferation. Conversely, spermidine supplementation improved renal function, reduced fibrosis by 75.3%, and decreased senescent regions by 74%. Mechanistically, AMD1 deficiency increased γH2AX-marked DNA damage and activated the p53/p21 checkpoint, whereas spermidine attenuated this response and restored DNA synthesis capacity. Collectively, tubular AMD1 acts as a metabolic checkpoint that preserves polyamine homeostasis to restrain p53/p21-dependent senescence, promote adaptive repair after AKI, and spermidine supplementation represents a potential strategy to mitigate maladaptive AKI-to-CKD progression. DOI: 10.1080/0886022X.2026.2680375 PMCID: PMC13267046 PMID: 42289383 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions P21

Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial.

1. J Med Econ. 2026 Dec;29(1):1258-1278. doi: 10.1080/13696998.2026.2646078. Epub 2026 Apr 21. Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial. Johansson E(1), Wilding JPH(2)(3), Upadhyay N(1), van Hest N(4), Kirk M(5), Spaepen E(6), Zimner-Rapuch S(1), Annemans L(7), Bays H(8). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. (2)Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. (3)Clinical Sciences Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. (4)Costello Medical, Bristol, UK. (5)Costello Medical, Manchester, UK. (6)HaaPACS GmbH, Schriesheim, Germany. (7)Interuniversity Center of Health Economic Research (ICHER), Department of Public Health and Primary Care, Ghent University, Ghent, Belgium. (8)Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky, USA. PURPOSE: This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]). PATIENTS AND METHODS: This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses. RESULTS: Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD). CONCLUSION: Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD). Plain Language Summary: This study focused on evaluating the cost-effectiveness of two weight management drugs, tirzepatide and semaglutide, for adults in the US who are overweight or have obesity. Using data from the SURMOUNT-5 trial, the analysis showed that tirzepatide was more effective and less costly, providing better weight loss and health benefits compared to semaglutide.The findings revealed that for every 1,000 individuals treated with tirzepatide, there were 70 fewer cases of type 2 diabetes and 10 fewer cases of heart disease compared to those treated with semaglutide. Additionally, patients on semaglutide experienced a longer duration living with moderate or severe sleep

Mentions Semaglutide

Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study.

1. J Med Econ. 2026 Dec;29(1):1111-1129. doi: 10.1080/13696998.2026.2646079. Epub 2026 Apr 22. Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study. Annemans L(1), Johansson E(2), Spaepen E(3), van Hest N(4), Grist J(5), Zimner-Rapuch S(2), Wilding JPH(6)(7). Author information: (1)Interuniversity Center of Health Economic Research (ICHER), Department of Public Health and Primary Care, Ghent University, Ghent, Belgium. (2)Eli Lilly and Company, Indianapolis, IN, USA. (3)HaaPACS GmbH, Schriesheim, Germany. (4)Costello Medical, Bristol, UK. (5)Costello Medical, London, UK. (6)Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. (7)Clinical Sciences Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. PURPOSE: This study presents an updated health economic model for evaluating the long-term cost-effectiveness of interventions in overweight and obesity, integrating new clinical evidence from the SURMOUNT clinical trial programme and methodological advancements in type-2 diabetes and obstructive sleep apnea (OSA) modelling. PATIENTS AND METHODS: An updated individual patient simulation model evaluated the costs and long-term clinical outcomes of tirzepatide (5, 10, 15.0 mg) versus diet and exercise (D&E) alone in patients with a body mass index (BMI) ≥30 kg/m2 (obesity), or BMI ≥27 to <30 kg/m2 (overweight) + ≥1 obesity-related complication with a UK healthcare perspective. Key improvements over a previously published model were introduced, including modelling remission and progression of OSA, capturing realistic patterns of D&E discontinuation, incorporating HbA1c as a continuous cardiometabolic endpoint and transition to R-based implementation over VBA. Primary results include incremental cost-effectiveness ratios (ICERs; cost/QALY), costs, life years gained and quality-adjusted life years (QALYs). Secondary outcomes including clinical outcomes, random seed and cohort convergence, deterministic sensitivity results and run time were also calculated. RESULTS: The refined model predicted that all tirzepatide doses were cost-effective compared to D&E at a £20,000/QALY gained WTP (willingness-to-pay) threshold (ICERs: £8,327-£10,157). Refined estimation of long-term D&E discontinuation and OSA remission likely contributed to lower incremental costs, higher QALYs, and reduced ICERs compared with the previous model, aligning outcomes more closely with expected benefits from weight management treatment. Transitioning to R-based implementation reduced run time (e.g. by 4.52 h for deterministic sensitivity analyses) and enhanced model stability in all analyses conducted. CONCLUSION: This enhanced economic model represents a significant advancement in the evaluation of obesity pharmacotherapy, designed to enhance clinical relevance, technical robustness, and increase usability. It supports evidence-based decision-making for chronic weight management treatment in the UK, and beyond, while offering a scalable platform for future therapeutic evaluations. Plain Language Summary: In this study, researchers improved a computer model that estimates how weight-loss treatments affect people’s health and healthcare costs over their lifetime. The model focuses on adults in the UK who are overweight or have obesity and at least one related health condition. It compares treatment with tirzepatide plus diet and exercise to diet and exercise alone. It builds on an earlier model but includes several important updates based on new clinical evidence and feedback from experts.The updated model more accurately reflects real-world health changes by tracking how weight loss affects conditions such as obstructive sleep apnea (a condition where breathing repeatedly stops and starts during sleep) and type 2 diabetes over t

Mentions Tirzepatide

Sauchinone attenuates UVB-induced photoaging by suppressing oxidative stress and ferroptosis through activation of the Keap1-Nrf2 pathway in dermal fibroblasts.

1. Pharm Biol. 2026 Dec;64(1):764-782. doi: 10.1080/13880209.2026.2668138. Epub 2026 May 21. Sauchinone attenuates UVB-induced photoaging by suppressing oxidative stress and ferroptosis through activation of the Keap1-Nrf2 pathway in dermal fibroblasts. Zhang X(1)(2), Wang J(1)(2), Zhou Y(1)(2), Shen C(1)(2), Yuan M(1)(2), Li Q(1)(2), Li W(3). Author information: (1)Shanghai Qiran Biotechnology Co., Ltd, Shanghai, PR China. (2)Shanghai Jinjia Technology Co., Ltd, Shanghai, PR China. (3)Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. CONTEXT: Skin photoaging induced by chronic ultraviolet B (UVB) exposure is primarily driven by oxidative stress. Emerging evidence suggests that ferroptosis contributes to UVB-induced skin damage. Sauchinone, a phenolic lignan derived from Saururus chinensis, possesses potent antioxidant and anti-inflammatory properties; however, its protective effects and underlying mechanisms against UVB-induced skin damage remain unclear. OBJECTIVE: This study aimed to investigate the potential photoprotective effects and underlying mechanisms of sauchinone against UVB-induced skin damage in dermal fibroblasts. MATERIALS AND METHODS: UVB-induced HFFs were used as an in vitro model of photoaging. Cellular senescence, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were evaluated using fluorescence staining, flow cytometry, qPCR, ELISA, and western blot analysis. RESULTS: Sauchinone significantly attenuated cellular senescence and ECM degradation in UVB-induced HFFs, as evidenced by reduced SA-β-gal activity and decreased expression of p16 and p21, increased COL1A1 levels, and decreased MMP1 levels. Sauchinone also alleviated oxidative stress by reducing intracellular ROS and MDA levels while restoring GSH content and antioxidant enzyme activity. In addition, sauchinone attenuated ferroptosis-related features, including reduced lipid ROS and Fe2+ accumulation, and normalized ACSL4, GPX4, FTH1, and SLC7A11 expression. Mechanistically, sauchinone was associated with activation of the Keap1-Nrf2 pathway, as evidenced by decreased Keap1 levels, enhanced nuclear translocation of Nrf2, and upregulation of downstream antioxidant genes. Importantly, pharmacological inhibition of Nrf2 using ML385 partially reversed the protective effects of sauchinone on oxidative stress, ferroptosis, cellular senescence, and ECM degradation. DISCUSSION AND CONCLUSIONS: Our findings revealed that sauchinone protected fibroblasts against UVB-induced photoaging by inhibiting oxidative stress and ferroptosis, potentially through activation of the Keap1-Nrf2 pathway. DOI: 10.1080/13880209.2026.2668138 PMCID: PMC13195707 PMID: 42165632 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. The funders had no role in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the paper.

Mentions P21

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

1. Ann Med. 2026 Dec;58(1):2663263. doi: 10.1080/07853890.2026.2663263. Epub 2026 Apr 30. Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. Lin Y(1)(2)(3), Wang Y(1)(2), Wang W(1)(2)(3), Deng Z(1)(2)(3), Zhang Y(1)(2), Peng Y(1)(2), Tang J(1)(2)(3), Li J(1)(2)(3), Huang C(1)(2)(3)(4), Jian D(1)(2)(3). Author information: (1)Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. (2)National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. (3)Hunan Key Laboratory of ageing Biology, Xiangya Hospital, Central South University, Changsha, China. (4)Department of Dermatology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention. DOI: 10.1080/07853890.2026.2663263 PMCID: PMC13134749 PMID: 42059427 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions P21

Lung microbiota dysbiosis mediates PM(2.5)-induced pulmonary inflammation through antibiotic-reversible mechanisms.

1. J Immunotoxicol. 2026 Dec;23(1):2660647. doi: 10.1080/1547691X.2026.2660647. Epub 2026 Apr 23. Lung microbiota dysbiosis mediates PM(2.5)-induced pulmonary inflammation through antibiotic-reversible mechanisms. Zheng Y(1), Zhang L(2)(3)(4), Tian J(2)(3)(4), Li N(2)(3)(4), Li Q(2)(3)(4), Li F(5), Meng J(5), Zhang Z(2)(6), Yun X(5), Duan S(1). Author information: (1)School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. (2)Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China. (3)Shandong Provincial Key Medical and Health Laboratory of Women's Occupational Exposure and Fertility Preservation, Jinan, China. (4)Jinan (Preparatory) Key Laboratory of Women's Diseases and Fertility Preservation, Jinan, China. (5)School of Public Health, North China University of Science and technology, Tangshan, China. (6)School of Public Health, Qingdao University, Qingdao, China. Fine particulate matter (PM2.5) exposure contributes to over 4 million premature deaths annually, yet the mechanistic role of lung microbiota in PM2.5-induced pulmonary inflammation remains poorly understood. In collaboration of 16S rRNA and single-cell RNA multi-omics analysis and in vivo/in vitro experimental validation with antibiotic intervention strategies, the study here examined PM2.5-microbiota interactions in murine PM2.5 exposure models and cellular systems. It was found that PM2.5 exposure induced lung microbiota dysbiosis characterized by Gram-negative bacterial expansion, particularly Proteobacteria dominance, accompanied by reduced microbial diversity. scRNA analysis revealed coordinated activation of TLR4/MyD88/NLRP3 inflammatory signaling pathways and p53/p21/p16-mediated cell cycle arrest. Moreover, PM2.5 exposure activated NLRP3 inflammosome-dependent macrophage pyroptosis as evidenced by increased interleukin (IL)-1β, IL-18, caspase-1, and GSDMD expression. In vitro studies demonstrated that the inflammatory changes induced by PM2.5 exposure were statistically indistinguishable from those of LPS-positive controls, confirming endotoxin-like mechanisms. Critically, antibiotic pretreatment effectively attenuated PM2.5-induced inflammatory responses, cell cycle arrest, and tissue pathology, which established causality between microbiota disruption and pulmonary dysfunction. In conclusion, this study revealed lung microbiota dysbiosis as a critical mediator of PM2.5-induced pulmonary inflammation through Gram-negative bacterial expansion and subsequent endotoxin-like activation of inflammatory cascades, thereby providing novel mechanistic insights and potential microbiome-targeted therapeutic strategies for air pollution-associated respiratory diseases. DOI: 10.1080/1547691X.2026.2660647 PMID: 42024669 [Indexed for MEDLINE]

Mentions P21

The epigenetic archaeology of human-dog companionship.

1. Epigenetics. 2026 Dec;21(1):2676911. doi: 10.1080/15592294.2026.2676911. Epub 2026 May 24. The epigenetic archaeology of human-dog companionship. Faraji J(1), Metz GAS(1)(2). Author information: (1)Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada. (2)Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, AB, Canada. Humans have coexisted with dogs for at least 20,000 years, yet the biological consequences of long-term human-dog co-residence remain poorly understood. We propose that sustained exposure to dogs may have contributed to context-dependent variation in human stress regulation, immune function, and socio-emotional neurobiology through environmentally responsive epigenetic mechanisms. Here, we define an epigenetic imprint as detectable differences in gene-regulatory marks, including DNA methylation at environmentally sensitive loci, consistent with developmental plasticity and early-life environmental calibration rather than germline inheritance. In this Commentary, we integrate evidence from genomics, neuroscience, microbiome research, evolutionary anthropology, and palaeoepigenetics to examine whether multispecies living environments may represent an under-recognised biological exposure shaping human regulatory biology. We further outline a framework to test whether archaeologically inferred dog co-residence is associated with epigenetic and regulatory signatures in ancient human populations while accounting for major ecological and demographic confounds. Overall, we argue that human-dog cohabitation provides a plausible and testable model for investigating how long-term social and ecological relationships may influence stress and immune regulation across populations. DOI: 10.1080/15592294.2026.2676911 PMCID: PMC13203029 PMID: 42177806 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions Oxytocin

Vaginal trial outcomes and emergency cesarean section factors among women with different classifications of hypertensive disorders of pregnancy.

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2648161. doi: 10.1080/14767058.2026.2648161. Epub 2026 May 5. Vaginal trial outcomes and emergency cesarean section factors among women with different classifications of hypertensive disorders of pregnancy. Zhang Y(1), Sun J(1), Shen J(1). Author information: (1)Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, Shenyang, China. BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a prevalent complication and a leading cause of maternal and perinatal mortality. While vaginal delivery is generally possible for most women with HDP, there is no standardized framework detailing variations in vaginal delivery outcomes across different HDP classifications or identifying the factors influencing emergency cesarean section (EmCS). OBJECTIVE: To explore the vaginal trial outcomes and risk factors associated with emergency cesarean section among women with different classifications of HDP. METHODS: This was a single-center retrospective cohort study of 894 pregnant women with HDP who underwent a vaginal trial. Of these, 584 were diagnosed with gestational hypertension, 216 with pre-eclampsia, and 94 with chronic hypertension. The study collected and compared detailed maternal and perinatal outcomes. RESULTS: (1) The success rate of vaginal delivery ranged from 85.1% to 90.8% across various classifications of HDP without significant differences. (2) Chronic hypertension was four times more likely to lead to intrapartum poorly controlled blood pressure than gestational hypertension. (3) Factors influencing EmCS in HDP included parity, antepartum BMI, labor induction, intrapartum fever, intrapartum antihypertensive use, and oxytocin during stages of labor. Parity served as an independent protective factor across all HDP classifications. Stratified analysis revealed that for gestational hypertension, risk factors included antepartum BMI ≥ 30 kg/m2, labor induction, and intrapartum antihypertensive use. For pre-eclampsia, oxytocin and intrapartum fever were risk factors. In chronic hypertension, antepartum BMI ≥ 30 kg/m2 and intrapartum fever were identified as risk factors, although the former was not significant. CONCLUSION: The success rate of vaginal trials across various classifications of HDP is high. Vaginal trial can impact intrapartum blood pressure, particularly for women with chronic hypertension. Tailored management strategies should include encouraging vaginal trial for multiparous women, control of antepartum BMI, judicious use of labor induction, and vigilant monitoring of hypertension and fever, with individualized evaluation and treatment based on HDP classification. DOI: 10.1080/14767058.2026.2648161 PMID: 42086488 [Indexed for MEDLINE]

Mentions Oxytocin

Retraction statement: carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery.

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2667973. doi: 10.1080/14767058.2026.2667973. Epub 2026 May 12. Retraction statement: carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery. [No authors listed] Retraction of J Matern Fetal Neonatal Med. 2016;29(8):1257-60. doi: 10.3109/14767058.2015.1043882. DOI: 10.1080/14767058.2026.2667973 PMID: 42120321

Mentions Oxytocin

GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.

1. Ann Med. 2026 Dec;58(1):2660386. doi: 10.1080/07853890.2026.2660386. Epub 2026 Apr 18. GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers. Chikatimalla R(1), Shah A(2), Shah T(3), Perry G(4), Banker H(5), Aggarwal K(6), Jain R(7). Author information: (1)Kamineni Institute of Medical Sciences, Narketpally, India. (2)GMERS Medical College, Gotri, Vadodara, India. (3)GMERS Medical College, Valsad, India. (4)Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. (5)Maulana Azad Medical College, New Delhi, India. (6)Dayanand Medical College and Hospital, Ludhiana, Punjab, India. (7)Division of Hospital Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. OBJECTIVES: To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. METHODS: A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. RESULTS: GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. CONCLUSION: GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management. Plain Language Summary: GLP-1 receptor agonist (GLP-1RA) therapy should be incorporated into a broad approach for risk reduction for stroke in patients with type 2 DM, especially in situations where prevention of ischaemic stroke is of high importance.Long-acting GLP-1 receptor agonists (e.g., semaglutide and dulaglutide) are preferred over shorter-acting preparations for their cerebrovascular protective effects, properties of which are more consistent and beneficial for the risk of ischaemia.GLP-1RA therapy could provide a special advantage to patients with multiple risk factors for cardiometabolic diseases such as obesity, hypertension, dyslipidemia and documented atherosclerotic cardiovascular disease.On the other hand, the neuroprotective properties of GLP-1RAs, which occur through anti-inflammatory, antioxidant, endothelial-stabilising or mitochondrial-protective actions, provide rationale for the use.Treatment should be individualised for renal function, tolerance, potential for compliance, cost and accessibility. This allows for maximal long-term cerebrovascular benefits. DOI: 10.1080/07853890.2026.2660386 PMCID: PMC13094292 PMID: 41999297 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the authors.

Mentions Semaglutide

A qualitative study exploring experiences about using semaglutide for weight loss in a rural setting in Denmark - 'she is probably on the meds'.

1. Scand J Prim Health Care. 2026 Dec;44(1):2636584. doi: 10.1080/02813432.2026.2636584. Epub 2026 Mar 16. A qualitative study exploring experiences about using semaglutide for weight loss in a rural setting in Denmark - 'she is probably on the meds'. Guldhammer A(1), Drivsholm T(1), Tomova-Olsen SA(1), Tranberg Jensen K(1). Author information: (1)The Section of General Practice and the Research Unit for General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. INTRODUCTION: Semaglutide has gained attention for its efficacy in weight loss. However, little is known about patients' experiences. This study explores patient experiences with using Semaglutide for weight loss (SEMA-WL) in a rural Danish context. METHODS: We conducted semi-structured interviews with nine participants from a rural Danish municipality, recruited from a local clinic. The sample included six women and three men, aged 33-65, who had been prescribed SEMA-WL for at least two months. Data was analysed using systematic text condensation. FINDINGS: We identified four themes. First, we highlight different experiences of negative perceptions from the local community for using SEMA-WL, often perceived as 'cheating' or as 'an easy way out'. Furthermore, we describe how SEMA-WL is experienced to provide more energy in the participants everyday lives but also viewed as a short-term intervention rather than a permanent solution, assisted by concerns of weight regain. Finally, we show how the participants continuously outweigh the risks of using new medication fearing potential long-term side effects versus living with obesity. CONCLUSION: The study highlights the complex social dynamics and personal experiences of using SEMA-WL. While medication offers benefits, it also presents challenges such as social stigma, concerns about long-term effectiveness and side effects, and financial costs. Future research should focus on investigating the experiences of using SEMA-WL in other and more diverse settings as well as the contact and information exchange between patients and healthcare providers. DOI: 10.1080/02813432.2026.2636584 PMCID: PMC12997375 PMID: 41838446 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions Semaglutide

Meox1 promotes hepatocellular carcinoma progression potentially via regulation of cell cycle and p21 expression.

1. Cell Adh Migr. 2026 Dec;20(1):2658289. doi: 10.1080/19336918.2026.2658289. Epub 2026 Apr 19. Meox1 promotes hepatocellular carcinoma progression potentially via regulation of cell cycle and p21 expression. Ruan J(1), Xie Y(2), Zhang C(3), Sun D(3). Author information: (1)Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shan'xi, People's Republic of China. (2)Hebei Key Laboratory of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, People's Republic of China. (3)The Liver Disease Center of PLA, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, People's Republic of China. Meox1 is aberrantly expressed in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the effects of Meox1 on HCC cells and explore the underlying molecular mechanisms. Cell proliferation, colony formation, migration, invasion, and cell cycle distribution were assessed by CCK-8, clonogenic, Transwell, and flow cytometry assays, respectively. Protein expression was examined by Western blotting. Meox1 silencing significantly inhibited proliferation, clonogenic capacity, migration and invasion of HCC cells. Cell cycle analysis showed a reduction in G1-phase cells with a marked accumulation in the G2 phase following Meox1 knockdown. Western blot analysis revealed that suppression of Meox1 reduced p21CIP1/WAF1 expression. Meox1 contributest to HCC progression and may represent a potential therapeutic target. DOI: 10.1080/19336918.2026.2658289 PMCID: PMC13097779 PMID: 42002886 [Indexed for MEDLINE] Conflict of interest statement: The authors have no relevant financial or non-financial interests to disclose.

Mentions P21

Hydrogen reshapes the senescent microenvironment of callus to enhance the healing of anti-osteoporotic-drug-induced atypical femoral fracture.

1. Biomaterials. 2026 Nov;334:124287. doi: 10.1016/j.biomaterials.2026.124287. Epub 2026 May 7. Hydrogen reshapes the senescent microenvironment of callus to enhance the healing of anti-osteoporotic-drug-induced atypical femoral fracture. An Y(1), Zhang H(2), Zhang Y(3), Zhang S(3), Zheng L(4), Shao H(3), Du W(5), Cheng L(6), Sun W(7), Ma J(6), Ruan Y(5), Xu J(8), Qin L(9). Author information: (1)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany. (2)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. (3)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. (4)Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences Limited, Hong Kong Special Administrative Region of China. (5)Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region of China. (6)Department of Orthopedics & Joint Surgery, National Center of Integrated Chinese and Western Medicine, Center for Osteonecrosis and Hip Dysplasia Preservation, China-Japan Friendship Hospital, Beijing, PR China. (7)Chengdu Hip and Femoral Head Hospital, Chengdu, PR China. (8)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: jiankunxu@cuhk.edu.hk. (9)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: lingqin@cuhk.edu.hk. Long-term bisphosphonates (BPs) are widely used to treat osteoporosis, however, they are paradoxically associated with the development of atypical femoral fractures (AFFs), which often characterized by impaired healing. In this study, we induced an AFF model using zoledronate (ZOL) administration in ovariectomized (OVX) osteoporotic rats, following a unilateral femoral fracture. Here we identified that a local pro-senescent microenvironment causes persistent inflammation and impairs effective regeneration in rat AFFs. Molecular hydrogen has demonstrated anti-senescence and anti-inflammatory properties, yet its effects on AFF healing remain unexplored. Therefore, we treated the AFF rats with hydrogen rich water (HRW). The outcomes were assessed by radiographs, histology, micro-CT, and biomechanical tests. The fr

Mentions P21

Yi-Qi-Jian-Pi formula alleviates hepatic fibrosis in acute-on-chronic liver failure by regulating ferritinophagy-mediated hepatic stellate cell senescence.

1. J Ethnopharmacol. 2026 Oct 28;369:121865. doi: 10.1016/j.jep.2026.121865. Epub 2026 May 15. Yi-Qi-Jian-Pi formula alleviates hepatic fibrosis in acute-on-chronic liver failure by regulating ferritinophagy-mediated hepatic stellate cell senescence. Chen J(1), Tang X(1), Fang M(1), Hu S(1), Wang J(1), Chen X(2), Xiao Q(2), Wang X(1), Xie F(3), Tan S(4). Author information: (1)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. (2)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. (3)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Liver Disease, Jinling Hospital affiliated to Medical College of Nanjing University, Nanjing, Jiangsu Province, 210001, China. Electronic address: rosemary1223@126.com. (4)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. Electronic address: fsyy01455@njucm.edu.cn. ETHNOPHARMACOLOGICAL RELEVANCE: Acute-on-chronic liver failure (ACLF) represents a severe clinical syndrome characterized by rapid exacerbation of chronic hepatic disease. Liver fibrosis (LF) significantly contributes to the advancement of ACLF pathology. The traditional Chinese medicine (TCM) preparation Yi-Qi-Jian-Pi formula (YQJPF) exhibits promising therapeutic effects on ACLF and LF; however, the underlying pharmacological mechanisms and active components remain incompletely understood. AIM OF THE STUDY: This study seeks to elucidate the pharmacodynamic properties, active constituents, and underlying mechanisms of YQJPF in treating liver fibrosis within an ACLF rat model, focusing specifically on ferritinophagy activation and the induction of hepatic stellate cell (HSC) senescence. MATERIALS AND METHODS: A rat model of ACLF was induced via combined administration of CCl4 and LPS/D-GalN, and an in vitro model was established using human hepatic stellate cells (LX2). Liver-targeted active components were characterized using UHPLC-Q-Orbitrap-MS/MS analysis, with network pharmacology utilized to predict critical molecular targets. NCOA4 siRNA and ferrostatin-1 were used to validate mechanism specificity. The therapeutic effects and associated mechanisms were systematically evaluated through biochemical assays, histopathological examinations, and molecular and cellular analyses. RESULTS: YQJPF improved liver histopathology and attenuated fibrosis and ACLF in rats. It inhibited viability and proliferation of LX2 cells, decreased TGF-β1 secretion, and downregulated α-SMA and Collagen I expression. UHPLC-Q-Orbitrap-MS/MS identified 82 liver-tropic components (including 50 prototypes and 32 metabolites) in rat liver tissues. Network pharmacology revealed 257 potential targets, with 135 overlapping with hepatic fibrosis-related targets (core targets included TP53, NCOA4, and CDKN2A). YQJPF induced HSC senescence (upregulated p16, p21, and HMGA1; downregulated TERT; triggered cell cycle arrest) and activated ferritinophagy (upregulated NCOA4, Beclin1, LC3BII/I; downregulated FTH1 and p62; increased ROS/iron accumulation). NCOA4 knockdown or Fer-1 treatment reduced YQJPF-induced HSC senescence and antifibrotic effects. CONCLUSION: YQJPF reduces ACLF-related LF by NCOA4-mediated ferritinophagy, which promotes HSC senescence. The 82 liver-tropic components and 135 overlapping targets highlight its multi-component, multi-target effects, providing a scientific foundation for its clinical application. Copyri

Mentions P21

Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.

1. Int J Cardiol. 2026 Sep 1;458:134560. doi: 10.1016/j.ijcard.2026.134560. Epub 2026 May 19. Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system. Estler B(1), Fröhlich H(1), Täger T(1), Heins J(1), Frey N(1), Frankenstein L(2). Author information: (1)Department of Cardiology, Angiology and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. (2)Department of Cardiology, Angiology and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: Lutz.Frankenstein@med.uni-heidelberg.de. BACKGROUND: Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability. METHODS: We developed a Markov model comparing tirzepatide versus placebo, both added to standard care, in the SUMMIT population from the German statutory health insurance perspective. The model used monthly cycles over 5 years with four Kansas City Cardiomyopathy Questionnaire clinical summary score-defined health states (Q1-Q4) plus death. Arm-specific transitions and rates of all-cause death and worsening heart failure were derived from SUMMIT. Deterministic and probabilistic sensitivity analyses, including tirzepatide price-reduction scenarios, were conducted to explore parameter uncertainty and price thresholds simultaneously. A prevalence-based budget impact analysis extrapolated results to the German HFpEF-obesity population under alternative eligibility (SUMMIT-like vs broad) and uptake (30%, 50%, 100%) scenarios. RESULTS: Discounted per-patient costs were €5827 (placebo) and €31,052 (tirzepatide), with quality-adjusted life years of 3.539 and 3.638. Tirzepatide generated 0.100 additional quality-adjusted life years at an incremental cost of €25,225, yielding an incremental cost-effectiveness ratio of 252,611€/quality-adjusted life year, with low probability of cost-effectiveness at €100,000/QALY. Five-year incremental spending was ∼€1.9-6.2 billion with SUMMIT-like and ∼ €3.8-12.6 billion with broad eligibility, depending on uptake. CONCLUSIONS: Tirzepatide provides modest quality-adjusted life year gains at substantially higher costs and, at current price, appears neither cost-effective nor affordable at scale in German care. Substantial price reductions would be required to improve economic attractiveness and budgetary impact. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.ijcard.2026.134560 PMID: 42155673 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest NF declares “Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events” from Novo Nordisk. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijcard.2026.134560.

Mentions Tirzepatide

Atrazine alters kisspeptin signaling and downstream neuroendocrine regulation following embryonic exposure in zebrafish.

1. Toxicology. 2026 Sep;525:154503. doi: 10.1016/j.tox.2026.154503. Epub 2026 May 15. Atrazine alters kisspeptin signaling and downstream neuroendocrine regulation following embryonic exposure in zebrafish. Stradtman SC(1), Sathisaran U(1), Dierolf BK(1), Sumner G(1), Tamagno WA(1), Freeman JL(2). Author information: (1)School of Health Sciences, Purdue University, West Lafayette, IN, USA. (2)School of Health Sciences, Purdue University, West Lafayette, IN, USA. Electronic address: jfreema@purdue.edu. Atrazine is an herbicide used to control broadleaf and grassy weeds but is also a known endocrine disrupting chemical classified by the US EPA for its effect on the luteinizing hormone (LH) surge. The US EPA's maximum contaminant level (MCL) for atrazine in drinking water is 3 parts per billion (ppb; µg/L), though concentrations may exceed this during peak crop seasons. Because drinking water is the primary exposure route, studying environmentally relevant concentrations near the MCL is critical for understanding public health impacts. Atrazine has been shown in epidemiological and toxicological studies to disrupt neuroendocrine and reproductive functions, including suppression of gonadotropin-releasing hormone (GnRH) neuron activity, leading to decreased LH and follicle-stimulating hormone (FSH) surges. Given the breadth of observed effects, this study hypothesized that atrazine targets an upstream neuroendocrine regulator-the kisspeptin signaling pathway-due to its dual role in reproductive and dopaminergic regulation. Kisspeptin expression was characterized in developing zebrafish, showing increases every 24 h from 1 to 120 h post fertilization (hpf). Zebrafish were exposed during embryogenesis (1-72 hpf) to atrazine at 0, 0.3, 3, or 30 ppb. Immunofluorescence at 120 hpf showed reduced kisspeptin expression in the habenula at 3 ppb and near-complete loss of kiss1/kiss2 expression with brain disorganization at 30 ppb. Kisspeptin, LH, and FSH levels were measured at 168 hpf and 6 months post fertilization (mpf). Age- and sex-dependent alterations were observed. Behavioral tests revealed anxiety-like phenotypes in larvae and adults. These findings indicate atrazine disrupts neuroendocrine and behavioral function through kisspeptin pathway dysfunction. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.tox.2026.154503 PMID: 42142733 Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

GLP-1 receptor agonists and post-endovascular thrombectomy outcomes in acute ischemic stroke: a multicenter propensity score matched analysis.

1. J Clin Neurosci. 2026 Sep;151:112089. doi: 10.1016/j.jocn.2026.112089. Epub 2026 May 30. GLP-1 receptor agonists and post-endovascular thrombectomy outcomes in acute ischemic stroke: a multicenter propensity score matched analysis. Rai P(1), Bathla G(2), Praveen N(3), Kakadiya J(4), Dhaduk V(5), Chen HA(6), Salim HA(7), Azzam AY(8), Essibayi MA(9), Altschul DJ(10), Dmytriw AA(11), Yedavalli VS(12), Aggarwal E(13), Latifi S(14), Malhotra A(15), Colasurdo M(16), Gandhi D(17), Lakhani DA(18). Author information: (1)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: rai.pranjal@mayo.edu. (2)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: bathla.girish@mayo.edu. (3)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: niharika.praveen@outlook.com. (4)Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD, USA. Electronic address: jaykakadiya07@gmail.com. (5)Shantabaa Medical College and General Hospital, Amreli, India. Electronic address: vidhidhaduk1@gmail.com. (6)Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD, USA. Electronic address: alvin.huanwen.chen@gmail.com. (7)Department of Neuroradiology, MD Anderson Medical Center, Houston, TX, USA. Electronic address: hamza.sleeem@gmail.com. (8)Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: ahmedyazzam@gmail.com. (9)Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: m.amir.essibayi@gmail.com. (10)Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: daltschu@montefiore.org. (11)Neuroendovascular Program, Massachusetts General Hospital, Harvard University, Boston, MA, USA; Neurovascular Centre, Departments of Medical Imaging and Neurosurgery, St Michael's Hospital, Toronto, ON, Canada. Electronic address: adam.dmytriw@gmail.com. (12)Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD, USA. Electronic address: vyedava1@jhmi.edu. (13)Department of Endocrinology, Mayo Clinic, Rochester, MN, USA. Electronic address: Aggarwal.eishvauk@mayo.edu. (14)Department of Neurosciences, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: shahrzad.latifikhereshky@hsc.wvu.edu. (15)Department of Radiology, Yale New Haven Hospital, New Haven, CT, USA. Electronic address: ajay.malhotra@yale.edu. (16)Department of Interventional Radiology, Portland, OR, USA. Electronic address: mcolasurdo@gmail.com. (17)Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD, USA. Electronic address: dheeraj.gandhi@som.umaryland.edu. (18)Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: dhairyalakhani@gmail.com. BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1As) have demonstrated cardiovascular and cerebrovascular benefits in high-risk populations, but their impact in patients with acute ischemic stroke (AIS) requiring endovascular thrombectomy (EVT) remains uncertain. METHODS: We performed a retrospective cohort analysis using the TriNetX Network, identifying adults (≥18 years) with AIS treated with EVT from January 1, 2016 through December 31, 2025. Patients with GLP-1A exposure within three months prior to EVT constituted the exposure cohort; those without served as comparators. This pre-index window was specified to eliminate immortal time bias, with follow-up beginning on the EVT date for both cohorts. Three-year outcomes included all-cause mortality and inpat

Mentions Semaglutide

Semaglutide, at a dose that produces modest weight loss, induces mild suppression of bone remodeling in healthy control rats and those with chronic kidney disease.

1. Bone. 2026 Sep;210:117933. doi: 10.1016/j.bone.2026.117933. Epub 2026 May 12. Semaglutide, at a dose that produces modest weight loss, induces mild suppression of bone remodeling in healthy control rats and those with chronic kidney disease. Allen MR(1), Metzger CE(2), Chen NX(3), Tinsley IC(4), DiMarchi RD(4), O'Neill K(3), Matter EK(2), Moe SM(5). Author information: (1)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Roudebush VA, Indianapolis, IN, United States of America. Electronic address: matallen@iu.edu. (2)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America. (3)Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America. (4)Department of Chemistry, Indiana University, Bloomington, IN, United States of America. (5)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America. The effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment on bone are unclear. The goal of this study was to investigate the effects of semaglutide, a GLP-1RA, on bone structure, remodeling, and mechanical properties in healthy control animals and those with chronic kidney disease (CKD). Male Cy/+IU rats with progressive CKD and littermate controls were treated with escalating doses of semaglutide for 28 days. Endpoint measures included bone structure, assessed by micro-CT, bone remodeling, assessed by histomorphometry, and bone mechanical properties, assessed by 3-point bending tests. Semaglutide treatment led to reduced food intake and weight loss, with CKD rats receiving semaglutide having 15% lower body weight at the end of the study compared to untreated CKD rats, while control rats did not have a statistical difference in weight (-5%) at the end of the study. Muscle mass was also lower in semaglutide-treated animals compared to untreated groups. CKD led to higher blood urea nitrogen with no effect of semaglutide. Serum PTH was lower in control rats treated with semaglutide, but this effect was not seen in the CKD cohorts. There were also main effects of semaglutide on serum calcium and phosphorus levels. CKD resulted in lower trabecular bone volume and higher cortical porosity with no effect of semaglutide. Mineralizing surfaces from dynamic histomorphometry were lower in control rats treated with semaglutide compared to untreated control and bone formation rate also trended lower in semaglutide-treated animals (∼20%). CKD animals had lower mechanical properties; semaglutide effects were only noted in toughness. At doses causing mild weight loss, semaglutide modestly lowered trabecular bone remodeling with little interaction with CKD disease status. Published by Elsevier Inc. DOI: 10.1016/j.bone.2026.117933 PMID: 42128321 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew R. Allen reports financial support was provided by U.S. Department of Veterans Affairs. Matt Allen, Ian Tinsley, Richard DiMarchi reports a relationship with MBX Bioscience that includes: consulting or advisory and funding grants. Matt Allen, Richard DiMarchi reports a relationship with BWB Bioscience that includes: consulting or advisory and funding grants. Sharon Moe reports a relationship with Eli Lilly and Company that includes: equity or stocks. If there ar

Mentions Semaglutide

Corrigendum to "Associations of intrapartum synthetic oxytocin administration with reduced neonatal salivary oxytocin levels and altered sucking patterns" [Early Hum. Dev. 218 (2026) 106539].

1. Early Hum Dev. 2026 Sep;220:106584. doi: 10.1016/j.earlhumdev.2026.106584. Epub 2026 May 15. Corrigendum to "Associations of intrapartum synthetic oxytocin administration with reduced neonatal salivary oxytocin levels and altered sucking patterns" [Early Hum. Dev. 218 (2026) 106539]. Omaru M(1), Fujita F(2), Kajiwara S(2), Wakamatsu E(2), Kuroishi S(3), Ochiai Y(3), Morokuma S(4). Author information: (1)Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: omaru.machiko.348@m.kyushu-u.ac.jp. (2)Department of Nursing, Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, 812-8582, Japan. (3)Research & Development Division, Pigeon Corporation, Tokyo, 103-8480, Japan. (4)Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: morokuma.seiichi.845@m.kyushu-u.ac.jp. Erratum for Early Hum Dev. 2026 Jul;218:106539. doi: 10.1016/j.earlhumdev.2026.106539. DOI: 10.1016/j.earlhumdev.2026.106584 PMID: 42140803

Mentions Oxytocin

Oxytocin modulates glucose metabolism to protect against cardiac remodeling via the STAT3/eNOS Axis.

1. Cell Signal. 2026 Sep;145:112605. doi: 10.1016/j.cellsig.2026.112605. Epub 2026 May 15. Oxytocin modulates glucose metabolism to protect against cardiac remodeling via the STAT3/eNOS Axis. Zhao Y(1), Qian X(1), Wang Q(1), Wang Z(1), Fu N(1), Wang L(1), Feng R(1), Yang W(1), Bai X(2), Qian J(3), Yang Y(4). Author information: (1)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. (2)Department of Cardiac Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. (3)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. Electronic address: qianjinqiao@ydyy.cn. (4)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. Electronic address: yangyuqiao@ydyy.cn. Oxytocin (OT), an endogenous cardiovascular homeostatic hormone, is currently attracting considerable attention because it can improve energy metabolism and cardiac function. This study investigated whether OT mitigates cardiac remodeling in association with alterations in glucose metabolism. In vivo, cardiac hypertrophy and fibrosis were induced in C57BL/6 J mice via angiotensin II (Ang II), while in vitro H9c2 cardiomyoblasts and neonatal rat cardiac fibroblasts (NRCFs) were treated with Ang II or TGF-β1, respectively, with or without OT. We found that OT suppressed cardiac hypertrophy and fibrosis, increased ATP and glucose levels, reduced lactate accumulation, suppressed glycolysis, and enhanced glucose oxidation in cardiomyocytes. Mechanistically, OT upregulated its receptor and inhibited pyruvate kinase M2 (PKM2) in TGF-β1-stimulated NRCFs. In hypertrophic cardiomyocytes induced by Ang II, transcription factor STAT3 was activated and eNOS was downregulated, while OT suppressed STAT3 activation and nuclear translocation of p-STAT3, and enhanced the expression of eNOS. Either Stat3 overexpression or Nos3 downregulation attenuated OT's beneficial and metabolic effects. Additionally, we demonstrated that the transcription factor STAT3 is enriched at and interacts with the Nos3 promoter region. Overexpression of eNOS partially restored OT-associated protective effects that were attenuated by Stat3 overexpression. Collectively, these findings suggest that OT attenuates cardiac remodeling, at least in part, in association with modulation of glucose metabolism and the STAT3/eNOS pathway, providing mechanistic insight into its cardioprotective effects. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cellsig.2026.112605 PMID: 42142820 Conflict of interest statement: Declaration of competing interest The authors declare that they have no competing interests.

Mentions Oxytocin

Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study.

1. J Affect Disord. 2026 Aug 15;407:121802. doi: 10.1016/j.jad.2026.121802. Epub 2026 Apr 17. Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study. Aboukaoud M(1), Hoch B(2), Weiser M(3), Amiaz R(3). Author information: (1)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. (2)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. (3)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. INTRODUCTION: Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability. METHODS: We conducted a disproportionality analysis of the WHO VigiBase (2010-2024), including T2DM patients. Reports of depressed mood and suicidal thoughts associated with GLP-1RAs were compared with other glucose-lowering medications. Analyses incorporated age, sex, time-to-onset, dose, comorbid depression, and concomitant antidepressant use. Adjusted reporting odds ratios (RORs) and a Weibull time-to-event model were applied. Causality was explored using Bradford Hill criteria. RESULTS: A total of 1,183,817 adverse events related to GLP-1RA were identified. Depressed mood and suicidality signals were observed with semaglutide, liraglutide, and tirzepatide (adjusted ROR0.25: 2.13, 1.52, 1.07) and (adjusted ROR0.25: 6.76, 2.43, 3.39), respectively. No signal was identified for suicide attempts or completed suicide. Absolute reporting frequencies were low. Concomitant antidepressant use was 2.3-5 times more frequent, and comorbid depression 25%-120% higher, compared with other glucose-lowering medications. Median time-to-onset was 96 days. Survival analysis demonstrated an early increase in reporting followed by stabilization over time. Adjustment for antidepressant use modestly attenuated associations. CONCLUSION: GLP-1RAs were associated with increased reporting of depressed mood and suicidal thoughts, particularly in patients receiving concomitant antidepressants. These findings support a patient-centered model in which underlying affective vulnerability or reporting factors drive reported mood symptoms rather than a uniform drug-specific effect. GLP-1RAs remain clinically valuable, but psychiatric monitoring during early treatment in vulnerable patients is warranted. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.jad.2026.121802 PMID: 42002107 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors, Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser, and Revital Amiaz, have no conflicts of interest to declare and no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review.

1. Behav Brain Res. 2026 Aug 5;511:116262. doi: 10.1016/j.bbr.2026.116262. Epub 2026 May 14. Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review. Dutra JB(1), Gregorio T(1), Lorenzon F(1), Peixe CMS(2), Bernuci MP(3), Lima FB(4). Author information: (1)Departamento de Ciências Fisiológicas, Campus Trindade, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. (2)Programa de Pós-Graduação em Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. (3)Departamento de Fisiologia, ACF Centro Politécnico, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: marcelo.bernuci@ufpr.br. (4)Departamento de Ciências Fisiológicas, Campus Trindade, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. Electronic address: fernanda.lima@ufsc.br. BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disease associated with hyperandrogenism, which causes infertility and often leads to mental health disorders. Although gonadotropin-releasing hormone (GnRH) neuronal dysfunction may contribute to PCOS, the pathophysiology of mood disorders associated with the syndrome remains unclear. OBJECTIVE: We raise the question of whether imbalanced neurotransmitters controlling the mood state, such as GABA and monoamines, impact the reproductive neural circuit and may facilitate the emergence of mental health disorders in PCOS. METHODS: We systematically reviewed gene and protein expressions, and neurotransmitter contents related to GnRH signaling in studies of rats and mice models of PCOS. Searches were conducted through PubMed and Web of Science and 52 research articles were included. RESULTS: Our findings showed that the kisspeptinergic and noradrenergic signaling stimulates GnRH neurons in non-PCOS-like rodents. In contrast, serotonergic and GABAergic pathways exert receptor-dependent bidirectional effects, with distinct receptor subtypes mediating either inhibitory or excitatory influences. PCOS-like rodents present dysfunctional signaling to GnRH neurons, which is dependent on the PCOS model applied: i) postnatal androgenization leads to decreased kisspeptinergic, monoaminergic, and GABAergic signaling to GnRH neurons; ii) prenatal androgenization does not change kisspeptinergic signaling but monoaminergic and GABAergic alterations need further investigation in this model; iii) postnatal estrogenization results in reduced kisspeptinergic and GABAergic signaling, but the monoaminergic neurotransmission is increased in this model. CONCLUSION: The reduction in kisspeptinergic, monoaminergic, and GABAergic neurotransmission in postnatally androgenized rats and mice suggests that pathways regulating reproduction and mood may share underlying neurobiological mechanisms under an androgenic milieu. Whether this signaling is similarly altered in PCOS patients with mental health disorders remains to be determined. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.bbr.2026.116262 PMID: 42140496 [Indexed for MEDLINE]

Mentions Kisspeptin

Missense mutations in MKRN3 and central precocious puberty: a mutational approach to understanding protein function.

1. Curr Opin Pediatr. 2026 Aug 1;38(4):424-433. doi: 10.1097/MOP.0000000000001588. Epub 2026 Jun 8. Missense mutations in MKRN3 and central precocious puberty: a mutational approach to understanding protein function. Franssen D(1), Kaiser UB. Author information: (1)Division of Endocrinology, Diabetes, and Metabolism, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA. PURPOSE OF REVIEW: Loss-of-function mutations in MKRN3 are the most common monogenic cause of central precocious puberty (CPP), yet the functional consequences of missense variants, which account for the majority of such cases, remain incompletely understood. A growing body of genetic, biochemical, computational, and in vivo studies now allows a domain-by-domain dissection of how missense mutations impair MKRN3 function, offering mechanistic insight into pubertal regulation that extends beyond individual variant reporting. RECENT FINDINGS: Missense mutations in the C3HC4 RING finger domain consistently reduce ubiquitin ligase activity and impair MKRN3-mediated repression of neurokinin B, kisspeptin, and GnRH, while mutations in C3H zinc finger domains paradoxically enhance auto-ubiquitination or disrupt RNA binding, revealing distinct pathogenic mechanisms. Computational stability analysis shows that destabilizing and stabilizing variants can both be pathogenic, underscoring the limitations of in silico tools alone. Phenotypic variability is shaped by the classes of mutations, sexually dimorphic neuroendocrine sensitivity, epigenetic regulation of MKRN3 promoter activity, and polygenic modifiers of pubertal timing. SUMMARY: Understanding the domain-specific effects of MKRN3 missense mutations refines genotype-phenotype correlations and improves variant interpretation in clinical practice. Integration of functional assays with polygenic risk assessment is essential for accurate genetic counseling in families with CPP. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MOP.0000000000001588 PMID: 42290210 [Indexed for MEDLINE]

Mentions Kisspeptin

Tirzepatide ameliorates cisplatin-induced acute kidney injury by restoring NAMPT/NAD + homeostasis and enhancing Pink1-Parkin-mediated mitophagy.

1. Biochem Pharmacol. 2026 Aug;250(Pt 2):118040. doi: 10.1016/j.bcp.2026.118040. Epub 2026 May 9. Tirzepatide ameliorates cisplatin-induced acute kidney injury by restoring NAMPT/NAD + homeostasis and enhancing Pink1-Parkin-mediated mitophagy. Han C(1), Tan Z(2), Wang Y(3), Jing X(4), Cui X(5), Zhang Y(2), Yan P(2), Cheng Y(2), Yue H(2), Wang B(6), Guo H(7). Author information: (1)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China; Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. (2)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China. (3)Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. (4)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Laboratory of Shanxi Provincial People's Hospital, Taiyuan, 030012, China. (5)Department of Reproductive Medicine Center, Children's Hospital of Shanxi, The Affiliated Children's Hospital of Shanxi Medical University, Shanxi Maternal and Child Health Hospital, Taiyuan 030001, China. (6)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China. Electronic address: docwangbaodong@sxmu.edu.cn. (7)Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China; Department of Nephrology, Shenzhen Bao'an Shiyan People's Hospital, Shenzhen 518100, China. Electronic address: guohui8688@126.com. Mitochondrial dysfunction and insufficient mitophagy are central to cisplatin-induced acute kidney injury (AKI). Tirzepatide, a dual GLP‑1/GIP receptor agonist, exhibits reno-protective effects, but its mechanism related to mitochondrial homeostasis remains unclear. Here, we used metabolomics, in vivo mouse AKI model, and in vitro cisplatin-injured HK‑2 cells to explore the protective effects and underlying mechanisms. Tirzepatide pretreatment significantly alleviated renal dysfunction, tubular injury, and mitochondrial damage caused by cisplatin. Metabolomic analysis revealed that tirzepatide strongly regulated energy metabolism and autophagy , particularly NAD + homeostasis. Mechanistically, tirzepatide boosted NAD+ levels by nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme for NAD + synthesis , which in turn activating the Pink1-Parkin mitophagy pathway. Inhibition of autophagy or NAMPT abolished the mitochondrial and reno-protective effects of tirzepatide. Taken together, our findings demonstrate that tirzepatide protects against cisplatin‑induced AKI by enhancing NAMPT‑dependent NAD + restoration and promoting mitophagy, highlighting a promising therapeutic strategy for chemotherapy‑related nephrotoxicity. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.bcp.2026.118040 PMID: 42114682 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Tirzepatide

Molecular targets of oleoylethanolamide in the pathogenesis of alcohol use disorder: Mechanisms of central and peripheral action.

1. Alcohol. 2026 Aug;134:9-23. doi: 10.1016/j.alcohol.2026.04.004. Epub 2026 Apr 18. Molecular targets of oleoylethanolamide in the pathogenesis of alcohol use disorder: Mechanisms of central and peripheral action. Ivashkevich D(1), Manzhulo I(2). Author information: (1)A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041, Vladivostok, Russia. (2)A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041, Vladivostok, Russia. Electronic address: i-manzhulo@bk.ru. Alcohol use disorder (AUD) is a complex disease whose pathogenesis involves profound neurobiological disturbances in reward, stress, and cognitive control systems, as well as systemic peripheral pathological processes, including inflammation and organ damage. Oleoylethanolamide (OEA) - an endogenous lipid mediator synthesized from oleic acid, with the nuclear receptor PPAR-α as its primary target. Accumulated evidence indicates the multi-level therapeutic potential of OEA in correcting key aspects of AUD. Its central action importantly involves the ability to modulate dopaminergic transmission in the reward system and influence the balance of orexin and oxytocin signaling pathways, contributing to a reduction in motivation to consume alcohol. A significant aspect of its activity is its antidepressant and anxiolytic properties, associated with the normalization of monoaminergic neurotransmitter activity and the hypothalamic-pituitary-adrenal (HPA) axis during withdrawal. A substantial contribution to OEA's therapeutic profile is its pronounced anti-inflammatory and neuroprotective action, including strengthening of the intestinal barrier, suppression of neuroinflammatory cascades, and stimulation of neurotrophic support. Furthermore, OEA demonstrates hepatoprotective potential aimed at reducing steatosis, oxidative stress, and inflammation in the liver. Thus, the multi-organ mechanism of action of OEA corresponds to the multifactorial nature of AUD, justifying its consideration as a promising basis for developing comprehensive therapeutic strategies. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.alcohol.2026.04.004 PMID: 42009176 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Exogenous Kisspeptin-10 inhibits ovarian cancer progression through targeting the SP1-hTERT-ZEB1 regulatory axis.

Mentions Kisspeptin

Transforming a protease inhibitor into a peptide Guardian: BBI-armed hydrogel beads for Oral delivery of active peptides.

1. Food Res Int. 2026 Jul 31;236:119229. doi: 10.1016/j.foodres.2026.119229. Epub 2026 Apr 20. Transforming a protease inhibitor into a peptide Guardian: BBI-armed hydrogel beads for Oral delivery of active peptides. Xu Q(1), Li W(1), An J(2), Li J(1), Liu X(2), Li H(3). Author information: (1)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China. (2)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China; Key Laboratory of Plant Protein Innovation and Resource Development, China National Light Industry, Beijing Technology and Business University, Beijing 100048, China. (3)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China. Electronic address: lihe@btbu.edu.cn. This study repurposes the Bowman-Birk inhibitor (BBI), traditionally viewed as an antinutritional factor for its protease inhibition, as a protective agent for peptide therapeutics. We co-encapsulated BBI with semaglutide in hydrogel beads to orchestrate their release, thereby leveraging protease inhibition to enhance peptide stability. In vitro studies with ionically crosslinked beads showed that BBI release effectively inhibited trypsin. Crucially, this extended semaglutide's intestinal residence time from 2.5 to 4 h (1.6-fold increase over control, p < 0.05), showcasing a direct protective benefit. Release kinetics revealed a temporal synergy: early-phase BBI release (60% within 2 h) established a low-protease environment enabling sustained semaglutide release. Our findings not only offer a novel strategy for oral peptide delivery but also redefine antinutritional factors as valuable functional excipients in drug formulation. Copyright © 2024. Published by Elsevier Ltd. DOI: 10.1016/j.foodres.2026.119229 PMID: 42116484 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Neuroendocrine mechanisms of stress-induced KNDy-GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction.

1. Front Neuroendocrinol. 2026 Jul 4:101270. doi: 10.1016/j.yfrne.2026.101270. Online ahead of print. Neuroendocrine mechanisms of stress-induced KNDy-GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction. Bo W(1), Li Y(1), Wang R(1), Qiao X(1), Zhong Y(1), Liu T(1), Liang J(1), Lai H(1), Huang W(2). Author information: (1)Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China; NHC Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China. (2)Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China; NHC Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: weihuang64@163.com. Chronic stress disrupts female reproductive function, but the central mechanisms linking stress exposure to altered gonadotropin-releasing hormone (GnRH) pulsatility remain incompletely defined. The arcuate kisspeptin/neurokinin B/dynorphin (KNDy) network is a core component of the GnRH pulse generator, yet it functions within an expanded regulatory system involving fast amino-acid neurotransmission, steroid feedback, nitric oxide signaling, glial communication, metabolic cues, and stress-responsive neuropeptides. This review synthesizes evidence showing how hypothalamic-pituitary-adrenal (HPA)-axis activation may suppress KNDy-GnRH output. Corticotropin-releasing hormone, glucocorticoids, gonadotropin-inhibitory hormone/RFamide-related peptide-3, glial inflammatory mediators, serotonergic input, and energy-sensitive neuropeptides may converge to impair GnRH pulse-generator function. We further discuss the relevance of these mechanisms to functional hypothalamic amenorrhea, stress-sensitive polycystic ovary syndrome (PCOS) phenotypes, and developmental versus adult stress exposure. Overall, stress-induced reproductive dysfunction is best understood as disrupted network-level neuroendocrine rhythm regulation. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.yfrne.2026.101270 PMID: 42401315 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug-Drug Interactions for Orforglipron, a Small Molecule Glucagon-Like Peptide-1 Receptor Agonist.

1. Clin Pharmacol Ther. 2026 Jul 3. doi: 10.1002/cpt.70377. Online ahead of print. Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug-Drug Interactions for Orforglipron, a Small Molecule Glucagon-Like Peptide-1 Receptor Agonist. Morse BL(1), Coutant DE(1), Ma X(1), Raha S(1), Aithal K(1), Nicoll C(1), Rougée LRA(1), Bhattachar S(1). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. Orforglipron is an orally administered, small-molecule glucagon-like peptide-1 receptor agonist in clinical development for the treatment of type 2 diabetes and obesity. Orforglipron is a substrate of CYP3A4, organic anion transporting polypeptides (OATPs) 1B/1B3, and P-glycoprotein (P-gp); however, precipitants commonly used to define these mechanisms have not been fully characterized. The enzyme- and transporter-mediated DDI profile of orforglipron and that of CYP3A4/OATP1B/P-gp precipitants were characterized in six phase 1 clinical studies in healthy participants. Orforglipron pharmacokinetics were assessed with clarithromycin, carbamazepine, cyclosporine, and quinidine. Precipitant effects on CYP3A and OATP1B activity were measured using midazolam and coproporphyrin-I (CP-I). Orforglipron effects on CYP3A, P-gp, BCRP, and OATP1B were evaluated using midazolam, digoxin, rosuvastatin, simvastatin, atorvastatin, and CP-I. Mechanistic interrogation of the simvastatin interaction was also conducted. Clarithromycin, carbamazepine, and quinidine had minimal effect on CP-I pharmacokinetics, while the cyclosporine effect was substantial. Cyclosporine and quinidine weakly increased midazolam exposure. Orforglipron exposure increased in the presence of clarithromycin and cyclosporine and decreased with carbamazepine, demonstrating orforglipron exposure is affected by precipitants of CYP3A4 and OATP1B. Quinidine did not meaningfully change orforglipron exposure. Orforglipron had no clinically meaningful effect on the exposure of midazolam, digoxin, or atorvastatin. A weak increase in rosuvastatin exposure was consistent with BCRP inhibition, as CP-I data confirmed orforglipron does not affect OATP1B. Increase in simvastatin acid exposure was attributed to the unique disposition of simvastatin rather than enzyme or transporter inhibition. These findings address mechanistic precipitant knowledge gaps and provide a framework for managing potential orforglipron DDIs in clinical practice. © 2026 Eli Lilly and Company. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. DOI: 10.1002/cpt.70377 PMID: 42399716

Mentions Orforglipron

Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight.

1. Diabetes Obes Metab. 2026 Jul;28(7):5803-5809. doi: 10.1111/dom.70783. Epub 2026 Apr 17. Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight. Ma X(1), Li YG(1), Raha S(1), Sperry DC(1), Coutant DE(1), Bhattachar S(1). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. AIMS: To evaluate the bioequivalence of orally administered orforglipron tablets and capsules in participants with obesity or overweight who were otherwise healthy. MATERIALS AND METHODS: This phase 1, multicenter, open-label, multiple-dose, dose-escalation study was conducted in 429 healthy adults. Study participants received each orforglipron capsule and tablet dose strength once daily for 7 days in the fasted state at capsule doses of 1, 3, 6, 12, 24, or 36 mg and corresponding tablet doses of 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg. The primary endpoint was steady-state area under the concentration-time curve from 0 to 24 h (AUC0-24,ss) and steady-state maximum observed drug concentration (C max,ss). A prespecified mixed scaling approach was applied to evaluate bioequivalence. Safety and tolerability of the tablets and capsules were also assessed. RESULTS: Bioequivalence was demonstrated between capsules and dose-adjusted tablets across all six doses. The 90% confidence interval of the ratios of the geometric least-squares means of AUC0-24,ss and C max,ss between each capsule dose and corresponding tablet dose met the predefined criteria for bioequivalence. The safety profiles were similar between tablets and capsules, with no apparent differences or trends in the incidence of treatment-emergent adverse events by presentation or with increasing dose. CONCLUSIONS: Once-daily orforglipron capsules and dose-adjusted tablets demonstrated pharmacokinetic bioequivalence at all tested doses and showed similar safety and tolerability profiles, with mostly mild treatment-emergent adverse events consistent with previous orforglipron clinical trials. ClinicalTrials .gov Identifier: NCT06440980. © 2026 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70783 PMCID: PMC13243956 PMID: 41994902 [Indexed for MEDLINE] Conflict of interest statement: Xiaosu Ma, Ying Grace Li, David C. Sperry, David E. Coutant and Shobha Bhattachar are employees of Eli Lilly and Company and may be shareholders. Sohini Raha was an employee of Eli Lilly and Company at the time the described work was conducted and is now an employee of Novartis.

Mentions Orforglipron

Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

1. Diabetes Obes Metab. 2026 Jul;28(7):5761-5766. doi: 10.1111/dom.70742. Epub 2026 Apr 16. Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis. Lu Y(1), Chen J(1), Guo Y(1), Ding H(1), Liu YL(2), Van Name MA(3), Sharifi M(4), Lu Y(5)(6), Chen Y(7). Author information: (1)Ividence Inc, Newark, Delaware, USA. (2)UT Southwestern Medical Center, Peter O'Donnell Jr. School of Public Health, Dallas, Texas, USA. (3)Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (4)Section of General Pediatrics, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (5)Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. (6)Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. (7)The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AIMS: To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA). MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component. RESULTS: Nineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63). CONCLUSIONS: Higher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70742 PMCID: PMC13243969 PMID: 41992023 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Orforglipron

Development of an electrochemiluminescence immunoassay for quantitative determination of semaglutide in human serum.

1. Anal Biochem. 2026 Jul;714:116115. doi: 10.1016/j.ab.2026.116115. Epub 2026 Mar 21. Development of an electrochemiluminescence immunoassay for quantitative determination of semaglutide in human serum. Luo Y(1), Zhang J(1), Chen W(1), Zhang H(2), Zou L(3). Author information: (1)Wenzhou Medical University, Wenzhou City, 325024, Zhejiang province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China. (2)Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China. Electronic address: hefengzhang@ucas.ac.cn. (3)Wenzhou Medical University, Wenzhou City, 325024, Zhejiang province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China; Wenzhou KanryBio Biotech Co., Ltd, Wenzhou City, 325038, Zhejiang province, China. Electronic address: Michael_zou@ucas.ac.cn. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely used in the treatment of patients with type 2 diabetes mellitus and obesity. A sensitive and reliable quantification method is essential for bioanalysis of semaglutide in clinical studies. To develop a sensitive and specific immunoassay, we have prepared a pair of highly specific anti-semaglutide monoclonal antibodies and subsequently employed them as critical reagents in the development of an electrochemiluminescence immunoassay (ECLIA) for the quantification of semaglutide levels in human serum. The assay validation data presented here demonstrate that the performance of the ECLIA method meets prespecified criteria for all validation parameters within the quantitative range of 0.5 ng/mL to 200.0 ng/mL. The intra- and inter-assay precision (%CV) are both ≤14.4%, and accuracy (%RE) ranges from -12.5% to 15.3%. No interference is found with recombinant human GLP-1 as the endogenous counterpart, confirming the assay specificity. Additional assay performance parameters, including selectivity, dilutional linearity, hook effect, and sample stability, all meet the acceptance criteria preset in accordance with international guidelines for bioanalytical method validation. The method is suitable for bioanalysis of semaglutide in human serum. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.ab.2026.116115 PMID: 41871707 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.

1. Clin Chim Acta. 2026 Jun 27:121207. doi: 10.1016/j.cca.2026.121207. Online ahead of print. Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche. Banerjee AA(1), Bhanarkar SR(1), Kashikar S(1), Keshwani R(2), Walia S(2), Kavya DR(2), Bombe S(1), Pande S(1), Modi DN(1), Pathak BR(1), Joshi B(1), Tandon D(1), Patil A(1), Begum S(1), Mahale SD(1), Rao S(3), Surve SV(4). Author information: (1)ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400 012, India. (2)Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai 400 012, India. (3)Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai 400 012, India. Electronic address: c_sudha@hotmail.com. (4)ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400 012, India. Electronic address: surves@nirrch.res.in. BACKGROUND: Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are key regulators of GnRH secretion and may serve as surrogate biomarkers. We evaluated whether these neuropeptides, alone or in combination with basal gonadotropins, could provide clinically useful discrimination of ICPP and PT. METHODS: In this prospective study, Indian girls aged 6-9 years were enrolled as controls (n = 40), ICPP (n = 33), and PT (n = 23). Anthropometry, basal LH, FSH, estradiol, pelvic ultrasonography, and plasma Kp-10, NKB, and NPY levels were assessed. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Logistic regression models assessed incremental predictive value: Model 1 included the Kp-10/basal LH ratio; Model 2 added bone age advancement (BA-CA); and Model 3 further included basal estradiol. Clinical utility was examined using decision curve analysis (DCA). RESULTS: Anthropometric parameters did not differ between ICPP and PT. Kp-10 and NKB levels were higher in both early-puberty groups than controls, but neither marker alone discriminated ICPP from PT. The composite Kp-10/basal LH ratio showed superior performance, with an ROC-derived cut-off <4.07 ng/mIU (sensitivity 72.7%, specificity 87.0%, accuracy 78%). All three models showed similar discrimination (AUC 0.78-0.79), with no meaningful improvement after adding BA-CA or estradiol. DCA demonstrated a higher net benefit for the Kp-10/basal LH ratio compared with treat-all or treat-none strategies across clinically relevant thresholds. CONCLUSION: The Kp-10/basal LH ratio provides robust discrimination and meaningful clinical utility in differentiating ICPP from PT and may reduce reliance on GnRH stimulation testing. Copyright © 2026. Published by Elsevier B.V. DOI: 10.1016/j.cca.2026.121207 PMID: 42364891 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

Kisspeptin-2 stimulates testicular function in adult pejerrey (Odontesthes bonariensis): Does it act directly on the testes?

Mentions Kisspeptin

Efficacy and safety of orforglipron in obesity with type 2 diabetes mellitus: a GRADE-assessed meta-analysis of randomized controlled trials.

1. Diabetol Metab Syndr. 2026 Jun 26. doi: 10.1186/s13098-026-02218-9. Online ahead of print. Efficacy and safety of orforglipron in obesity with type 2 diabetes mellitus: a GRADE-assessed meta-analysis of randomized controlled trials. Emara A(1), Emara M(1), Mansour A(1), Elkholy MH(2), Abbas OF(1), Abdul-Hafez HA(3), Azzawi MADA(4), Shubietah A(5). Author information: (1)Faculty of Medicine, Al-Azhar University, Cairo, Egypt. (2)Faculty of Medicine, Alexandria National University, Alexandria, Egypt. (3)Department of Medicine, An-Najah National University, Nablus, West Bank, Palestine. hamzaakrm12@gmail.com. (4)Faculty of Medicine, The National Ribat University, Khartoum, Sudan. (5)Department of Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL, USA. BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) frequently coexist and markedly increase cardiometabolic risk. Orforglipron is a novel oral glucagon-like peptide-1 receptor agonist developed to improve adherence compared with injectable therapies. We performed a systematic review and meta-analysis to evaluate its efficacy and safety. METHODS: PubMed, Scopus, Cochrane CENTRAL, and Web of Science were searched through January 2026 for randomized controlled trials (RCTs) comparing orforglipron with placebo in adults with obesity and T2DM. Random-effects models were used to pool mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Three RCTs, including 2,505 participants, were analyzed. Dose-subgroup analyses demonstrated a consistent dose-response pattern across all efficacy outcomes. For body weight, reductions versus placebo ranged from MD - 2.43% at 3 mg to MD - 7.80% at 24 mg. BMI reductions ranged from MD - 0.88 kg/m² at 3 mg to MD - 2.70 kg/m² at 45 mg. Waist circumference reductions were significant at doses ≥ 6 mg, reaching MD - 5.90 cm at 24 mg. HbA1c reductions ranged from MD - 0.80% at 3 mg to MD - 1.67% at 45 mg, and fasting serum glucose reductions ranged from MD - 20.62 mg/dL at 3 mg to MD - 44.80 mg/dL at 45 mg. Treatment discontinuation due to adverse events was higher with orforglipron across doses, while serious adverse events were not significantly different from placebo at any dose. CONCLUSIONS: Orforglipron may improve weight and glycemic outcomes in obese patients with T2DM; however, these findings are based on only three randomized controlled trials, and several key efficacy outcomes were rated as low certainty, so the results should be interpreted cautiously pending larger confirmatory studies. © 2026. The Author(s). DOI: 10.1186/s13098-026-02218-9 PMID: 42363271 Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. AI use: The authors confirm that no artificial intelligence was used. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Mentions Orforglipron

Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices.

1. Analyst. 2026 Jun 22. doi: 10.1039/d6an00455e. Online ahead of print. Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices. Mazzarino M(1), Colpaert T(1), Deventer K(1), Van Eenoo P(1). Author information: (1)Doping Control Laboratory, Department of Diagnostic Sciences, Ghent University, Block B, Ottergemsesteenweg 460, BE-9000, Ghent, Belgium. monica.mazzarino@ugent.be. Recently, methods for detecting small peptides in dried blood spots have been published. These procedures typically involve multiple sample preparation steps, resulting in labor-intensive and costly workflows. In the present study, we report a fast, streamlined, and harmonized analytical workflow to detect 54 prohibited peptidic and non-peptidic compounds in dried blood spots, serum, and plasma. Sample preparation is based on a single microextraction step using 500 µL of a methanol/water (8 : 2, v/v) mixture. Detection was performed using liquid chromatography coupled with high-resolution mass spectrometry. The validation results showed satisfactory performance with respect to selectivity (no interferences were detected at the retention times of the analytes), detection limits (0.05-1.25 ng mL-1), carry-over (no signals in the negative sample injected after the positive sample), matrix effect (5-33%), extraction yield (15-80%), and extract stability (the target analytes were stable for at least 72 h in the autosampler at 10 °C). The method was successfully applied to samples containing sub-ng levels of ibutamoren, confirming that the analytical procedure presented in this study is fit for purpose within the doping-control framework. Stability studies showed that all compounds were stable (variation lower than 15%) for at least two months at -20 °C in all the blood matrices considered. At 4 and 22 °C, alexamorelin, AOD9604, buserelin, hGH 176-191, kisspeptin-10 and LHRH were extensively degraded after one week in serum and plasma, whereas BPC-157, TB500, vasopressin, lypressin, and terlipressin showed complete degradation only in serum. In contrast, in dried matrices all compounds remained detectable throughout the entire duration of the study, indicating that samples can be transported and stored under non-refrigerated conditions, thereby reducing costs. DOI: 10.1039/d6an00455e PMID: 42328738

Mentions Kisspeptin

A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation.

1. Nat Commun. 2026 Jun 20. doi: 10.1038/s41467-026-74598-5. Online ahead of print. A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation. Neve V(#)(1), Fernandois D(#)(2), Rai S(1), Özorhan Ü(1), Nampoothiri S(2), Ternier G(2), Sideromenos S(3), Gallet S(2), Allet C(2), Stahr M(1), Klaus N(1), Martinez-Corral I(2), Coêlho CFF(2), Chandrasekar A(1), Constantinescu A(1), Rivagorda M(1), Dührkop S(1), Cases Bazarra J(1), Binder S(1), Giacobini P(2), Rasika S(2), Nogueiras R(4), Harkany T(3)(5), Schwarz MK(6), Müller-Fielitz H(1), Prevot V(7), Schwaninger M(8). Author information: (1)Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck, Germany. (2)University Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France. (3)Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria. (4)Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain. (5)Department of Neuroscience, Karolinska Institutet, Solna, Sweden. (6)Institute for Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Bonn, Germany. (7)University Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France. vincent.prevot@inserm.fr. (8)Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck, Germany. markus.schwaninger@uni-luebeck.de. (#)Contributed equally Tanycytes are radial-glia-like cells that play important roles in regulating the neuroendocrine system and metabolism. Synapse-like (synaptoid) connections have previously been described between neurons and tanycytes, but their structure and function are unclear. Here, we report that neuron-tanycyte synaptoids are abundant and resemble typical neuronal synapses in shape and composition. Tanycytic subtypes receive specific inputs from a variety of hypothalamic as well as extrahypothalamic neuronal populations and respond to several neurotransmitters and neuromodulators. As proof-of-principle of their functional relevance, we demonstrate in mice, that two distinct populations of kisspeptin neurons, which stimulate the gonadotropic axis, innervate different tanycytic subsets of the mediobasal hypothalamus to control basal levels of the gonadotropin luteinizing hormone (LH) and its pulsatile release pattern, in a sex‑ and region‑specific manner. Neuron-tanycyte synaptoid connections are thus widespread, diverse and functionally specific elements of hypothalamic neural circuits that play a key role in finetuning hormonal axes. © 2026. The Author(s). DOI: 10.1038/s41467-026-74598-5 PMID: 42323316 Conflict of interest statement: Competing interests: The authors declare no competing interests.

Mentions Kisspeptin

Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine.

1. Drug Test Anal. 2026 Jun 19. doi: 10.1002/dta.70104. Online ahead of print. Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine. Krug O(1)(2), Thomas A(1), Thevis M(1)(2). Author information: (1)Institute of Biochemistry, Center for Preventive Doping Research (ZePräDo), German Sport University Cologne, Cologne, Germany. (2)European Monitoring Center for Emerging Doping Agents (EuMoCEDA), Cologne/Bonn, Germany. Tesofensine (NS-2330) is a pharmacologically active compound with weight-reducing effects in obese patients. Although still under regulatory review, it has been marketed online as a dietary supplement promoted for weight management and metabolic enhancement. Due to its impact on body weight, tesofensine could be relevant in competitive sports, particularly in weight-class disciplines and sports where power-to-weight ratio is decisive. It is classified under "S6 stimulants" on the World Anti-Doping Agency's Prohibited List and is prohibited in-competition only, making detailed knowledge of its metabolism and excretion essential for anti-doping purposes. Although the pharmacological effects and elimination of tesofensine and one dealkylated metabolite were described previously, elimination profiles and structural information on additional metabolites have been limited. In this study, in vitro metabolism experiments were conducted, followed by investigation of urinary metabolism and elimination in six volunteers after ingestion of 483 μg tesofensine as a dietary supplement. Urine was collected for up to 600 h, prepared by solid-phase extraction, and analyzed by LC-HRMS. Four principal metabolites were identified: three dealkylated metabolites (M1-M3) and one hydroxylated and glucuronidated metabolite (M4), supported by MS/MS dissociation patterns. The validated analytical method for human urine showed an LOD of 0.01 ng/mL, 34% recovery, and 8% interday imprecision. Marked interindividual variability was observed, with peak concentrations of 1-4 ng/mL after 4-46 h and detection windows up to 500 h. The findings enhance analytical procedures and suggest that recommended dosing is unlikely to result in concentrations constituting an Adverse Analytical Finding (AAF) under currently applicable stimulant minimum reporting levels. © 2026 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd. DOI: 10.1002/dta.70104 PMID: 42320973

Mentions Tesofensine

Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial.

1. Contemp Clin Trials Commun. 2026 Jun 19;52:101660. doi: 10.1016/j.conctc.2026.101660. eCollection 2026 Aug. Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. Malhotra A(1), Gottlieb DJ(2), Kundel V(3), Woehrle H(4), Chakladar S(5), Firmino Goncalves L(5), Calamai G(5). Author information: (1)University of California San Diego, La Jolla, CA, USA. (2)Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. (3)Icahn School of Medicine at Mount Sinai, New York, NY, USA. (4)Lung Center Ulm, Ulm, Germany. (5)Eli Lilly and Company, Indianapolis, IN, USA. INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent, yet current treatment remains limited. Poor adherence to positive airway pressure (PAP) and barriers associated with injectable therapies can limit potential therapeutic options for moderate-to-severe OSA. The SURMOUNT-OSA trials demonstrated that tirzepatide contributes to OSA severity improvements; however, the injectable mode of administration introduces barriers that may limit accessibility and long-term adherence. Orforglipron, a once daily oral glucagon-like-peptide-1 receptor agonist, may offer a more feasible and accepted therapeutic option. ATTAIN-OSA was developed to evaluate the efficacy and safety of oral orforglipron in adults with moderate-to-severe OSA. METHODS: ATTAIN-OSA is a master protocol with two multicenter, randomized, double-blind, placebo-controlled Phase 3 trials enrolling adults with moderate-to-severe OSA and obesity or overweight. Study 1 includes participants unable or unwilling to use PAP. Study 2 includes participants who use PAP and complete a protocol-mandated washout before baseline polysomnography. Participants are randomly assigned to placebo or orforglipron capsule formulation at maximum tolerated dose (12, 24, or 36 mg) for 52 weeks following a standardized dose escalation schedule. RESULTS: The primary endpoint is change in Apnea-Hypopnea Index (AHI) at Week 52. Key secondary endpoints include sleep apnea-specific hypoxic burden, Patient-Reported Outcomes Measurement Information System sleep-related impairment, high-sensitivity C-reactive protein, and body weight, and other AHI-related endpoints. Overall, 712 participants have been randomized to orforglipron or placebo (Study 1, n = 363; Study 2, n = 349). CONCLUSION: ATTAIN-OSA evaluates if once-daily oral orforglipron can provide an effective and more accessible therapeutic approach to treat moderate-to-severe OSA in adults with obesity or overweight. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06649045. © 2026 The Authors. Published by Elsevier Inc. DOI: 10.1016/j.conctc.2026.101660 PMCID: PMC13316212 PMID: 42383207 Conflict of interest statement: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Atul Malhotra reports financial support was provided by University of California San Diego (UCSD). Atul Malhotra reports a relationship with Eli Lilly that includes: consulting or advisory. Dr. Malhotra is funded by the NIH, including PI on R01 AG063925, R01 HL148436, R01 HL148436, R01 HL157985, R01 HL166485. He reports income from Livanova, Zoll, Sunrise, Eli Lilly and Company, and Powell Mansfield. He is co-founder and has equity in Clairyon a small startup related to predictive analytics. Resmed provided a philanthropic donation to UCSD in 2015. Livia Firmino Goncalves reports administrative support, statistical analysis, and writing assistance were provided by Eli Lilly and Company. Livia Firmino Goncalves reports a relationship with Eli Lilly and Company that includes: employment, equity or stocks, and non-financial support. Daniel J. Gottlieb reports financial support was provided by Eli Lilly and Company. Daniel J. Gottlieb reports a relations

Mentions Orforglipron

Obstetrical and medical outcomes following GLP-1 receptor agonist exposure in pregnancy: a case series.

1. Case Rep Womens Health. 2026 Jun 18;51:e00831. doi: 10.1016/j.crwh.2026.e00831. eCollection 2026 Sep. Obstetrical and medical outcomes following GLP-1 receptor agonist exposure in pregnancy: a case series. Wong K(1)(2), Al-Amri H(1), Werlang A(1). Author information: (1)Division Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Newborn Care, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. (2)Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada. The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has increased over the past several years. The resulting improved blood sugar control and optimized body weight ultimately improve fertility. Thus, it is increasingly common to have individuals inadvertently becoming pregnant while using GLP-1 RAs. This case series describes outcomes following the inadvertent use of GLP-1 RAs in the first trimester of pregnancy, including the incidence of major malformations, maternal glucose control and gestational weight gain. This case series included individuals receiving obstetric care at a tertiary perinatal center who had exposure to a GLP-1 RA between 2 months preconception to pregnancy conclusion for any indication or duration. Electronic medical records of participants were reviewed for fetal, obstetrical, maternal, and neonatal outcomes. There were 16 patients in the series. All had spontaneous and unplanned conception of singleton pregnancies while using subcutaneous semaglutide and continued administration during a part of the first trimester. All included patients were overweight or obese. No individual lost weight in pregnancy. No major fetal anomalies were identified. Following discontinuation of semaglutide, diabetes control required both metformin and insulin for most patients. There was one instance of iatrogenic preterm birth at 35 weeks for preeclampsia. The rate of preeclampsia was 18.8%. Given the high rate of obesity, there was a lower-than-expected rate of excessive gestational weight gain (37.5%). Further studies on the safety and possible benefits of GLP-1 RAs in pregnancy are required. © 2026 The Authors. Published by Elsevier B.V. DOI: 10.1016/j.crwh.2026.e00831 PMCID: PMC13310638 PMID: 42376629 Conflict of interest statement: The authors declare that they have no competing interest regarding the publication of this case report.

Mentions Semaglutide

Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity: Mechanistic pathways, clinical signals, and a monitoring framework.

1. Obes Pillars. 2026 Jun 18;19:100290. doi: 10.1016/j.obpill.2026.100290. eCollection 2026 Sep. Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity: Mechanistic pathways, clinical signals, and a monitoring framework. Simancas-Racines D(1), Campuzano-Donoso M(1), Rossetti G(2), Cobellis L(3), Pilone V(4), Fascì-Spurio F(5), Jima Gavilanes D(6), Soria C(7), Reytor-González C(1), Schiavo L(8). Author information: (1)Facultad de Ciencias de la Salud y Bienestar Humano, Universidad Tecnológica Indoamérica, Ambato, 180150, Ecuador. (2)General and Bariatric Surgery Unit, Abano Terme Policlinic, Padova, 35031, Italy. (3)Unit of General Surgery, Casa Di Cura "Prof. Dott. Luigi Cobelli", Vallo della Lucania, 84078, Italy. (4)Public Health Department, University of Naples Federico II, Naples, 80131, Italy. (5)Gastroenterology Unit, Ospedale dell'Angelo, Venice, Italy. (6)Escuela de Medicina, Universidad Espíritu Santo, Samborondón, 0901952, Ecuador. (7)Hospital de Lima Este Vitarte, Ctra. Central KM 7.5, Ate, 15491, Peru. (8)Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Baronissi, 84081, Italy. BACKGROUND: Incretin-based pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have transformed obesity management by producing substantial weight loss through appetite suppression, reduced energy intake, and gastrointestinal effects. These mechanisms may also modify dietary intake, gastrointestinal physiology, and weight-loss-related metabolic adaptations, raising concern about micronutrient disturbances during long-term treatment. METHODS: This narrative clinical review synthesizes evidence on mechanistic pathways, clinical signals, and monitoring considerations related to micronutrient risk during incretin-based obesity pharmacotherapy. Evidence was integrated from dietary studies, observational cohorts, mechanistic investigations, clinical trials, pharmacovigilance reports, and literature on obesity-related micronutrient physiology. RESULTS: Micronutrient vulnerability appears to arise from the interaction between reduced food intake, lower dietary diversity, gastrointestinal intolerance, delayed gastric emptying, rapid weight loss, and baseline nutritional risk. The most relevant signals involve hematologic, fat-soluble, bone-related, trace element, and electrolyte domains, particularly iron, vitamin B12, vitamin D, calcium, magnesium, zinc, with additional context-dependent concerns involving thiamine, folate, vitamin A, other fat-soluble vitamins and potassium. Most abnormalities reported to date are subclinical or indirect, but clinically meaningful consequences may occur in susceptible individuals, including those with prior bariatric surgery, gastrointestinal disorders, poor baseline diet quality, older age, or prolonged nausea and vomiting. CONCLUSION: Micronutrient risk during incretin-based obesity pharmacotherapy is likely multifactorial and patient-specific. Individualized nutritional assessment and targeted laboratory monitoring should be considered for high-risk patients, while prospective studies are needed to define incidence, clinical relevance, and evidence-based monitoring strategies. © 2026 The Authors. DOI: 10.1016/j.obpill.2026.100290 PMCID: PMC13316283 PMID: 42382663 Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Semaglutide

Benefits and Harms of Pharmacologic Treatments in Adults With Overweight or Obesity: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

1. Ann Intern Med. 2026 Jun 16. doi: 10.7326/ANNALS-24-03764. Online ahead of print. Benefits and Harms of Pharmacologic Treatments in Adults With Overweight or Obesity: A Living Systematic Review and Network Meta-analysis for the American College of Physicians. Damen JAA(1), Idema DL(1), Vernooij RWM(1), Huis In 't Veld LF(1), Kusters MPT(1), Lokerse ME(1), de Kanter E(1), Spijker R(1), van der Braak K(1), Jenniskens K(1), Oerbekke MS(1), Hooft L(1). Author information: (1)Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, and American College of Physicians Center for Evidence Reviews, Philadelphia, Pennsylvania (J.A.A.D., D.L.I., R.W.M.V., L.F.H.V., M.P.T.K., M.E.L., E.d.K., R.S., K.v.d.B., K.J., M.S.O., L.H.). BACKGROUND: Overweight and obesity are closely linked to diseases such as type 2 diabetes, coronary heart disease, and stroke and have been shown to increase mortality risk. PURPOSE: To conduct a living systematic review of pharmacologic treatments for weight management in overweight or obesity in adults. DATA SOURCES: MEDLINE and Cochrane Central Register of Controlled Trials until October 2025. STUDY SELECTION: Randomized controlled trials that compared pharmacologic treatments for weight management (dulaglutide, exenatide, liraglutide, lixisenatide, naltrexone-bupropion, orforglipron, phentermine, phentermine-topiramate, retatrutide, semaglutide, semaglutide-cagrilintide, tirzepatide, or any combination with or without lifestyle intervention [LI]) for overweight or obesity (body mass index ≥25 kg/m2) in adults for outcomes such as mortality, weight loss, and quality of life. DATA EXTRACTION: One reviewer extracted data and assessed risk of bias and certainty of the evidence; a second reviewer verified these data. DATA SYNTHESIS: The review included 69 studies with a total of 112 511 participants. Thirty-seven studies were at low risk of bias. In meta-analyses, nearly all studied interventions were more effective than placebo and/or LI in reducing weight, but more discontinuations due to adverse events were observed. Semaglutide probably reduced mortality and major adverse cardiovascular events (MACE), and both semaglutide and tirzepatide led to the greatest weight loss compared with placebo and/or LI in pairwise and network meta-analyses. Evidence for outcomes such as mortality, MACE, and serious adverse events was limited. LIMITATION: Direct head-to-head comparisons of different treatments were limited. CONCLUSION: Nearly all studied interventions were more effective than placebo and/or LI in reducing weight. Semaglutide and tirzepatide showed the most favorable results across outcomes. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42023491646). DOI: 10.7326/ANNALS-24-03764 PMID: 42296503 Conflict of interest statement: Disclosures: Disclosure forms are available with the article online.

Mentions Retatrutide

Hierarchical regulation and mechanism of "open-hollow-fibrous network" structures: Osteogenic-angiogenic coupling responses of poly(γ-benzyl-L-glutamate) microspheres.

1. Biomater Adv. 2026 Jun 15;188:215017. doi: 10.1016/j.bioadv.2026.215017. Online ahead of print. Hierarchical regulation and mechanism of "open-hollow-fibrous network" structures: Osteogenic-angiogenic coupling responses of poly(γ-benzyl-L-glutamate) microspheres. Su J(1), Zhang Y(2), Cao Y(1), Ren T(1), Zhang K(3), Chen D(4), Yin J(5). Author information: (1)School of Materials Science and Engineering, Shanghai University, Shanghai, 200444, People's Republic of China. (2)Department of Endodontics, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai 200001, People's Republic of China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, People's Republic of China. (3)School of Materials Science and Engineering, Shanghai University, Shanghai, 200444, People's Republic of China. Electronic address: zhangkunxi@shu.edu.cn. (4)Department of Endodontics, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai 200001, People's Republic of China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, People's Republic of China. Electronic address: chendong@fudan.edu.cn. (5)School of Materials Science and Engineering, Shanghai University, Shanghai, 200444, People's Republic of China. Electronic address: jbyin@oa.shu.edu.cn. Biomimetic fibrous microspheres with a high specific surface area hold substantial promise for bone tissue engineering. In this study, asymmetric open-hollow nanofibrous microspheres (HNMs) were fabricated from polypeptide poly(γ-benzyl-L-glutamate) (PBLG) via a combination of emulsion and thermally induced phase separation, yielding PBLG HNMs. To further impart biofunctionality, the copper peptide (GHK-Cu) was covalently grafted onto the microspheres to obtain osteoinductive and pro-angiogenic PBLG-GCu HNMs. The optimized microspheres exhibited an average diameter of 372 ± 102 μm, which is suitable for injectability, and an opening size of 219 ± 53 μm, enabling efficient cellular infiltration. The internal surface featured an interconnected nanofibrous network with a fiber diameter of 417 ± 78 nm, mimicking the extracellular matrix (ECM) microenvironment and providing abundant cell-interactive sites. Live/Dead staining and CCK-8 assays confirmed the cytocompatibility of the PBLG-GCu HNMs. Compared with non-functionalized PBLG HNMs, PBLG-GCu HNMs enhanced bone marrow mesenchymal stem cell (BMSC) mineralization and upregulated osteogenic gene expression, with Runx2, OPN, and OCN expression increased by 1.61-, 3.53-, and 2.29-fold, respectively. In addition, the tube formation assay verified robust angiogenic stimulation. Overall, the PBLG-GCu HNMs integrated hierarchical structural biomimicry with dual osteogenic-angiogenic bioactivity, exhibiting great potential as injectable scaffolds for repairing irregular bone defects. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.bioadv.2026.215017 PMID: 42320090 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions GHK-Cu

Semaglutide and major adverse cardiovascular events in patients with and without DM: A systematic review and meta-analysis.

1. Biomed Rep. 2026 Jun 12;25(2):92. doi: 10.3892/br.2026.2165. eCollection 2026 Aug. Semaglutide and major adverse cardiovascular events in patients with and without DM: A systematic review and meta-analysis. Li Y(1), Lv C(1), Cao L(1), Lihua S(1), Ma Y(1). Author information: (1)Emergency Department of Dongying People's Hospital, Dongying, Shandong 257092, P.R. China. Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), has been associated with cardiovascular benefits, whereas the consistency of its effect across various clinical settings, as well as its safety-economic profile, remains uncertain. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were searched up to January 2025 and identified 11 randomized controlled trials (12 comparisons; 25,067 participants) comparing semaglutide with placebo or active control. Using a DerSimonian-Laird random-effects model, semaglutide reduced major adverse cardiovascular events by 32% [pooled odds ratio (OR)=0.68; 95%; confidence interval 0.52-0.91; 95% prediction interval 0.44-1.04]. Point estimates remained unchanged after censoring all STEP obesity trials (OR=0.70) or both heart-failure trials (OR=0.66), indicating a negligible institution-level effect. Mixed-effects meta-regression analysis revealed greater benefit with lower body weight, LDL- and total cholesterol levels, and lesser benefit with higher age, HbA1c and blood pressure (all P<0.01). Safety pooling found higher risks of any gastrointestinal (GI) disorder [relative risk (RR)=1.47], gallbladder events (RR=2.37), and discontinuation due to GI intolerance (RR 2.32). A total of seven out of 11 trials enrolled ≥75% White patients, none of whom were from low-income countries, limiting generalizability. Besides, U.S. cost-utility models published in the literature report incremental cost-effectiveness ratios of US$ 180,000-260,000 per quality-adjusted life-year, above conventional willingness-to-pay thresholds. Overall, semaglutide demonstrated marked cardiovascular risk reduction at all doses and across all populations, with low statistical heterogeneity. However, this benefit must be weighed against GI intolerance, limited racial and geographic representation and uncertain cost-effectiveness outside high-income regions. Future trials must oversample underrepresented minorities, extend to low- and middle-income regions, and include formal economic evaluations to further refine population-specific benefit-risk profiles and value estimates. Copyright: © 2026 Li et al. DOI: 10.3892/br.2026.2165 PMCID: PMC13284603 PMID: 42339050 Conflict of interest statement: The authors declare that they have no competing interests.

Mentions Semaglutide

GLP-1 Agonists in Adolescent Obesity: A Narrative Review of Single, Dual, and Triple Agonists.

1. Diabetes Metab Syndr Obes. 2026 Jun 12;19:566414. doi: 10.2147/DMSO.S566414. eCollection 2026. GLP-1 Agonists in Adolescent Obesity: A Narrative Review of Single, Dual, and Triple Agonists. Abid M(1), Sheikh KS(1), Ahmad MS(2), Jiang H(1). Author information: (1)Department of Metabolism and Endocrinology, Endocrine and Metabolic Disease Center, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People's Republic of China. (2)Department of Internal Medicine, Lahore General Hospital, Ameer-Ud-Din Medical College, Lahore, Punjab, Pakistan. Adolescent obesity is an escalating global health concern associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and long-term metabolic complications. Although lifestyle interventions remain first-line therapy, their limited long-term effectiveness has led to increasing interest in pharmacological approaches. This narrative review evaluates the mechanisms, clinical efficacy, and safety of glucagon-like peptie-1 (GLP-1) receptor agonists, as well as emerging dual and triple incretin-based therapies, in the management of adolescent obesity. A literature search was conducted using PubMed and Scopus, focusing on clinical trials, systematic reviews, and real-world studies published between 2010 and 2024. Evidence from pediatric and adolescent populations was prioritized, while adult data were included where adolescent-specific evidence remains unavailable and are interpreted cautiously. Among single-agent therapies, GLP-1 receptor agonists have demonstrated clinically meaningful weight reduction and metabolic benefits in adolescents. In the STEP TEENS trial, once-weekly semaglutide resulted in approximately 16% mean body weight reduction over 68 weeks, while liraglutide produced more modest reductions. Dual agonists such as tirzepatide and emerging triple agonists, including retatrutide, have shown superior weight-loss efficacy in adult populations; however, pediatric data for these agents remain limited or unavailable. Across all incretin-based therapies, gastrointestinal adverse effects are the most commonly reported side effects. In conclusion, GLP-1 receptor agonists represent an effective pharmacological option for adolescents with obesity, while dual and triple incretin agonists offer promising future therapeutic potential. Nevertheless, the clinical application of multi-receptor agonists in adolescents requires caution, as long-term safety, developmental outcomes, and real-world adherence data in pediatric populations are still lacking. Further well-designed pediatric trials are essential before broader adoption can be recommended. © 2026 Abid et al. DOI: 10.2147/DMSO.S566414 PMCID: PMC13271900 PMID: 42318576 Conflict of interest statement: The authors declare no competing interests.

Mentions Retatrutide

Retatrutide: Triple acting jab for type 2 diabetes lowers blood sugar and boosts weight loss, trial reports.

1. BMJ. 2026 Jun 9;393:e102036. doi: 10.1136/bmj-2026-102036. Retatrutide: Triple acting jab for type 2 diabetes lowers blood sugar and boosts weight loss, trial reports. Lang K(1). Author information: (1)Bristol. DOI: 10.1136/bmj-2026-102036 PMID: 42264536

Mentions Retatrutide

Comparative Effectiveness and Safety of Once-Weekly Injectable Semaglutide Versus Dulaglutide in Individuals with Type 2 Diabetes Managed in UK Primary Care: A Population-Based Cohort Study.

1. Lancet Reg Health Eur. 2026 Jun 8;67:101738. doi: 10.1016/j.lanepe.2026.101738. eCollection 2026 Aug. Comparative Effectiveness and Safety of Once-Weekly Injectable Semaglutide Versus Dulaglutide in Individuals with Type 2 Diabetes Managed in UK Primary Care: A Population-Based Cohort Study. Ulrich FS(1)(2), Frost Nielsen M(3)(4), Napoli N(5)(6)(7), Burden AM(1)(8). Author information: (1)Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. (2)Department of Mathematics, ETH Zurich, Zurich, Switzerland. (3)Department of Endocrinology, Odense University Hospital, Odense, Denmark. (4)Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark. (5)Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy. (6)Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico University of Rome, Rome, Italy. (7)Division of Bone and Mineral Diseases, Washington University, St Louis, MO, USA. (8)Division of Clinical Immunology and Rheumatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. BACKGROUND: The SUSTAIN-7 trial demonstrated greater HbA1c and bodyweight reductions with once-weekly semaglutide versus dulaglutide in type 2 diabetes, but strict eligibility criteria limit external validity. We evaluated the comparative real-world effectiveness and safety of these agents in UK primary care. METHODS: Using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, a Cegedim Database, we included adults with type 2 diabetes initiating semaglutide or dulaglutide between 01-Jan-2019 and 01-Dec-2022, followed through 30-Jun-2023. Co-primary outcomes were 1-year changes in HbA1c and bodyweight, estimated using a new-user, active-comparator cohort design with marginal structural models and inverse probability of treatment weighting. Treatment heterogeneity was assessed in the primary per-protocol analysis by SUSTAIN-7 trial-eligibility. Safety events were assessed while-on-treatment. FINDINGS: Among 6616 new users, 4636 (70.1%) remained on-treatment and 1980 (29.9%) discontinued early. Semaglutide new users (n = 1901) achieved greater 1-year reductions than dulaglutide new users (n = 2735) in HbA1c (estimated treatment difference [ETD] -0.22 percentage points [95% CI -0.30, -0.15]) and bodyweight (ETD -1.92 kg [95% CI -2.91, -0.93]). While semaglutide's benefits were preserved across the 87.7% (n = 4064) not meeting SUSTAIN-7 trial-eligibility (HbA1c: ETD -0.23 percentage points [95% CI -0.31, -0.15]; bodyweight: ETD -2.01 kg [95% CI -3.07, -0.95]), reductions in HbA1c and bodyweight were greater among trial-eligible individuals (12.3%; n = 572) for both agents (trial-eligible [semaglutide/dulaglutide] versus non-eligible [semaglutide/dulaglutide] individuals, HbA1c: -1.10/-1.02 versus -0.83/-0.60 percentage points; bodyweight: -5.72/-4.18 versus -5.50/-3.49 kg). Early discontinuers showed attenuated treatment effects and higher gastrointestinal event rates than those remaining on-treatment (23.5-26.1 versus 10.6-13.8 per 100 person-years). INTERPRETATION: New users of semaglutide achieved greater reductions in HbA1c and bodyweight than new users of dulaglutide with comparable safety, with benefits preserved across SUSTAIN-7 trial-eligible and non-eligible individuals, supporting preferential use of semaglutide in UK clinical practice. FUNDING: Swiss National Science Foundation. © 2026 The Author(s). DOI: 10.1016/j.lanepe.2026.101738 PMCID: PMC13262276 PMID: 42294355 Conflict of interest statement: All authors acknowledge support from the Swiss National Science Foundation for the submitted work. AMB and FSU do not declare any conflict of interest. MFN reports consultancy work for Novo Nordisk A/S; employment at Novo Nordisk A/S from June 2024 to February 2025; receipt of drugs for an investigator-initiated trial from Novo Nordisk A/S; and holds st

Mentions Semaglutide

Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-c

1. Lancet Diabetes Endocrinol. 2026 Jun 7:S2213-8587(26)00126-9. doi: 10.1016/S2213-8587(26)00126-9. Online ahead of print. Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. Aroda VR(1), Buzzetti R(2), Dalskov SM(3), Jain AB(4), Larsen JH(5), Mathieu C(6), Pratley RE(7), Videmark A(3), Watt T(3), Buse JB(8). Author information: (1)Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: varoda@bwh.harvard.edu. (2)Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. (3)Novo Nordisk, Søborg, Denmark. (4)Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Unity Healthcare, Surrey, BC, Canada. (5)Novo Nordisk, Aalborg, Denmark. (6)Department of Endocrinology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. (7)AdventHealth Translational Research Institute, Orlando, FL, USA. (8)Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. BACKGROUND: Cagrilintide-semaglutide (CagriSema) is a novel, once-weekly combination of the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. We aimed to assess the efficacy and safety of cagrilintide-semaglutide for people with type 2 diabetes inadequately controlled with diet and exercise. METHODS: REIMAGINE 1 was a randomised, double-blind, parallel-group, phase 3a study carried out at 42 sites (study sites included university hospitals, health-care centres, research centres, and other centres) in six countries. Adults aged 18 years or older with type 2 diabetes inadequately controlled with diet and exercise were randomly assigned (2:1:2:1) to receive once-weekly subcutaneous cagrilintide 2·4 mg plus semaglutide 2·4 mg (cagrilintide-semaglutide [2·4 mg each]), placebo 2·4 mg plus 2·4 mg, cagrilintide 1·0 mg plus semaglutide 1·0 mg (cagrilintide-semaglutide [1·0 mg each]), or placebo 1·0 mg plus 1·0 mg for 40 weeks. Randomisation was done using a web-based system with a block size of six and stratified according to HbA1c less than 8·5% at screening and participation in the MRI substudy. Participants, care providers, investigators, and outcome assessors were masked within dose level and all participants received visually identical injections to maintain masking throughout the study. The primary endpoint was change in HbA1c from baseline to week 40 in the full analysis set; safety was assessed in all participants who received at least one dose of the trial product. Change in bodyweight from baseline to week 40 was a prespecified secondary endpoint. This study is registered with ClinicalTrials.gov, NCT06323174, and is complete. FINDINGS: Between March 19 and Dec 5, 2024, 294 people were screened for eligibility, 189 of whom were enrolled and randomly assigned to cagrilintide-semaglutide (2·4 mg each; n=62), cagrilintide-semaglutide (1·0 mg each; n=63), or placebo (n=64). 103 (54%) of 189 were male, 86 (46%) were female, 147 (78%) were White, and 26 (14%) were Asian. Baseline mean HbA1c was 7·8% (SD 0·7) and BMI was 35·2 kg/m2 (7·4). Using the efficacy estimand, the estimated mean change in HbA1c after 40 weeks was -1·8 percentage points (SE 0·1) with cagrilintide-semaglutide (2·4 mg each), -1·5 percentage points (0·1) with cagrilintide-semaglutide (1·0 mg each), and -0·1 percentage points (0·2) with placebo. This corresponded to an estimated treatment difference of -1·7 percentage points (95% CI -2·0 to -1·3; p<0·0001) for cagrilintide-semaglutide (2·4 mg each) versus placebo and -1·3 percentage points (-1·8 to -0·9; p<0·0001) for cagrilintide-semaglutide (1·0 mg each) versus placebo. Cagrilintide-semaglutide was superior to placebo with respect to estimated mean relative change in bodyweight from

Mentions CagriSema

Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study.

1. Lancet. 2026 Jun 7:S0140-6736(26)01022-6. doi: 10.1016/S0140-6736(26)01022-6. Online ahead of print. Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Rosenstock J(1), Billings LK(2), Gajria R(3), Giorgino F(4), Johansen NB(3), Klein KR(5), Thamattoor UK(6), Buse JB(5), Jain AB(7). Author information: (1)Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: juliorosenstock@dallasdiabetes.com. (2)Department of Medicine, Endeavor Health (NorthShore Hospitals), Skokie, IL, USA; University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. (3)Novo Nordisk, Søborg, Denmark. (4)Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Puglia, Italy. (5)Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC, USA. (6)NXT-2, Bangalore, India. (7)TLC Diabetes and Endocrinology, Surrey, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Unity Healthcare, Surrey, BC, Canada. BACKGROUND: Basal insulin treatment for type 2 diabetes often results in inadequate glycaemic control and is associated with weight gain and increased risk of hypoglycaemia. We aimed to compare the efficacy and safety of a once per week combination of cagrilintide with semaglutide (CagriSema) versus placebo as an add-on to basal insulin in individuals with type 2 diabetes. METHODS: This double-blind, parallel-group, randomised, controlled, phase 3a study (REIMAGINE 3) was done at 46 centres (university hospitals, health-care centres, research centres, and other clinical trial sites) in six countries (the USA, China, Japan, Serbia, Slovakia, and South Africa). Adults with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0-10·5%) receiving stable once per day basal insulin with or without metformin were randomly assigned (2:2:1:1) to once per week subcutaneous cagrilintide 2·4 mg plus semaglutide 2·4 mg (hereafter cagrilintide-semaglutide [2·4 mg each]) or cagrilintide 1·0 mg plus semaglutide 1·0 mg (hereafter cagrilintide-semaglutide [1·0 mg each]) or dose-matched placebo (2·4 mg plus 2·4 mg or 1·0 mg plus 1·0 mg) for 40 weeks. Randomisation was stratified by HbA1c of less than 8·5% at screening (yes or no) and country (Japan; yes or no). Participants, care providers, investigators, and outcome assessors were masked within each dose level to treatment allocation, with active treatments visually identical to placebo. The primary endpoint was mean HbA1c change (percentage points) from baseline to week 40 in all participants randomly assigned to treatment; secondary endpoints included change in bodyweight and safety, including hypoglycaemia. This trial was registered with ClinicalTrials.gov (NCT06323161) and is complete. FINDINGS: Between March 26 and Nov 29, 2024, we screened 340 individuals and 274 were included and randomly assigned to cagrilintide-semaglutide (2·4 mg each; n=90), cagrilintide-semaglutide (1·0 mg each; n=93), or placebo (pooled; n=91). Mean baseline HbA1c was 8·8% (SD 1·0), 159 (58%) participants were male, and 115 (42%) were female. Mean HbA1c reductions were significantly greater with cagrilintide-semaglutide (2·4 mg each -2·33% [SE 0·08] and 1·0 mg each -2·10% [0·08]) versus placebo (-0·66% [0·11]) at week 40, using the efficacy estimand (estimated treatment difference for cagrilintide-semaglutide [2·4 mg each] vs placebo -1·68 percentage points [95% CI -1·95 to -1·41], p<0·0001; for cagrilintide-semaglutide [1·0 mg each] vs placebo -1·44 percentage points [95% CI -1·71 to -1·17], p<0·0001). Cagrilintide-semaglutide provided bodyweight reductions of 10-12%. Adverse events were reported by 72 (

Mentions CagriSema

Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study.

1. Lancet Diabetes Endocrinol. 2026 Jun 7:S2213-8587(26)00125-7. doi: 10.1016/S2213-8587(26)00125-7. Online ahead of print. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. Buse JB(1), Bajaj HS(2), Dalskov SM(3), Donaldson L(3), Hansen Duus HH(3), Fabricius TW(3), Haluzík M(4), Lingvay I(5), Pedersen SD(6), Pratley RE(7), Jain AB(8); REIMAGINE 2 study group. Author information: (1)Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: jbuse@med.unc.edu. (2)LMC Diabetes and Endocrinology, Brampton, ON, Canada. (3)Novo Nordisk, Søborg, Denmark. (4)Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. (5)Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. (6)C-ENDO Diabetes and Endocrinology Clinic and University of Calgary, Calgary, AB, Canada. (7)AdventHealth Translational Research Institute, Orlando, FL, USA. (8)Unity Healthcare, Surrey, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada. BACKGROUND: The amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide have complementary effects on glycaemic control and bodyweight. We aimed to investigate the efficacy and safety of a fixed-dose combination of cagrilintide and semaglutide (cagrilintide-semaglutide; known as CagriSema) versus semaglutide or cagrilintide for glycaemic control in people with type 2 diabetes and overweight or obesity. METHODS: REIMAGINE 2 was a randomised, double-blind, placebo-controlled and active-controlled, parallel-group study conducted in 30 countries (trial sites included university hospitals, health-care centres, research centres, and other centres). Participants aged 18 years or older with inadequately controlled type 2 diabetes (HbA1c 7·0-10·5% [53-91 mmol/mol]) receiving metformin with or without an SGLT2 inhibitor, and a BMI of 25 kg/m2 or more, were randomly assigned (8:8:2:8:8:1:1) to receive once-weekly subcutaneous cagrilintide 2·4 mg plus semaglutide 2·4 mg (hereafter cagrilintide-semaglutide [2·4 mg each]), semaglutide 2·4 mg, cagrilintide 2·4 mg, cagrilintide 1·0 mg plus semaglutide 1·0 mg (hereafter cagrilintide-semaglutide [1·0 mg each]), semaglutide 1·0 mg, or corresponding placebo for 68 weeks. Randomisation was done using a web-based system with blocked randomisation (block size 36) and stratification according to inclusion in the continuous glucose monitoring subgroup, HbA1c less than 8·5% at screening (yes or no), and country of participation (Japan; yes or no). The study participants, investigators, and study sponsor staff were masked to treatment allocation within dose level throughout the study. The primary endpoint was change in HbA1c from baseline to week 68 with cagrilintide-semaglutide (2·4 mg each) versus semaglutide 2·4 mg in the full analysis set; safety was assessed in all participants who received at least one dose of study product. This study is registered with ClinicalTrials.gov (NCT06065540) and is complete. FINDINGS: From Oct 10, 2023, to July 29, 2024, 3593 people were screened for eligibility, 2713 of whom were randomly assigned to cagrilintide-semaglutide (2·4 mg each; n=603), semaglutide 2·4 mg (n=605), cagrilintide 2·4 mg (n=152), cagrilintide-semaglutide (1·0 mg each; n=595), semaglutide 1·0 mg (n=609), or placebo (pooled 2·4 mg and 1·0 mg; n=149). 1164 (42·9%) of 2713 were female, 1549 (57·1%) were male, and 2207 (81·3%) were White. Of the randomly assigned participants, 2595 (95·7%) completed the study and 2376 (87·6%) were on treatment at week 68. Mean baseline HbA1c was 8·2%

Mentions CagriSema

Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.

1. Curr Obes Rep. 2026 Jun 6;15(1):44. doi: 10.1007/s13679-026-00722-7. Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure. Xie J(#)(1), Yang Y(#)(1), Chen W(#)(1), Wang L(1), Weng S(2), Lyu Q(1), Cao G(3). Author information: (1)School of Pharmacy, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, China. (2)Department of Endocrinology, Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China. (3)School of Pharmacy, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, China. caogang33@163.com. (#)Contributed equally PURPOSE OF REVIEW: Obesity stems from a chronic imbalance between energy intake and expenditure. Current therapeutic strategies primarily focus on reducing caloric intake, yet their long-term efficacy is often limited by compensatory metabolic adaptations that lead to weight regain. This review outlines the neural mechanisms through which the central nervous system regulates appetite and the peripheral metabolic pathways that drive adipose thermogenesis. Furthermore, it examines how integrated approaches-spanning from approved to preclinical and clinical-stage investigational agents (e.g., dual- or multi-target agonists), microbiome-targeted interventions (e.g., probiotics), and exercise therapy-can synergistically overcome the limitations of single-pathway strategies. Ultimately, this review provides a theoretical foundation for designing next-generation, personalized, multimodal obesity management regimens. RECENT FINDINGS: Traditional weight-loss drugs primarily act by centrally suppressing appetite, reducing food intake through modulation of neural circuits in regions such as the hypothalamus. However, studies show that relying on appetite suppression often triggers compensatory metabolic adaptation, ultimately leading to weight regain. Current anti-obesity drug development is therefore shifting toward integrated central-peripheral dual mechanisms. GLP‑1/glucagon dual-receptor agonists and triple-receptor agonists (such as retatrutide) have exhibited unprecedented weight-loss efficacy in clinical trials. These novel agents overcome the limitations of single-target appetite suppression by synergistically integrating central anorexigenic signaling with peripherally mediated increases in energy expenditure, thereby achieving more potent and durable weight reduction. The sustainability of obesity treatment relies on a dual-pronged intervention strategy: suppressing appetite to reduce energy intake while actively promoting energy expenditure, thereby overcoming the metabolic adaptation and weight rebound associated with monotherapy. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. DOI: 10.1007/s13679-026-00722-7 PMID: 42249250 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests.

Mentions Retatrutide

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blin

1. Lancet. 2026 Jun 6:S0140-6736(26)00967-0. doi: 10.1016/S0140-6736(26)00967-0. Online ahead of print. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Bajaj HS(1), Welch M(2), Shah P(3), Luna E(4), Jaouimaa FZ(5), Liu B(5), Liu R(5), Chen Y(5), Patel H(5), Bartee A(5). Author information: (1)LMC Diabetes and Endocrinology, Brampton, ON, Canada. Electronic address: harpreet.bajaj@lmc.ca. (2)Consano Clinical Research, San Antonio, TX, USA. (3)Gujarat Endocrine Centre, Ahmedabad, India. (4)Texas Valley Clinical Research, Weslaco, TX, USA. (5)Eli Lilly and Company, Indianapolis, IN, USA. BACKGROUND: Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone. METHODS: In this 40-week, phase 3, randomised, double-blind, placebo-controlled trial at 48 sites in the USA, Mexico, and India, we recruited adults (aged ≥18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA1c) between 7·0% and 9·5% (53-80 mmol/mol), and BMI of at least 23 kg/m2. Participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection. The primary endpoint was the change in HbA1c concentration from baseline to week 40. A key secondary endpoint was the percentage change in bodyweight from baseline to week 40. This trial is registered with ClinicalTrials.gov, NCT06354660, and is completed. FINDINGS: Between April 10, 2024, and April 21, 2025, 930 participants were screened and 537 (296 [55%] female and 241 [45%] male) were randomly assigned: 134 to retatrutide 4 mg, 133 to retatrutide 9 mg, 136 to retatrutide 12 mg, and 134 to placebo. Baseline mean age was 48·8 years (SD 12·1), mean HbA1c concentration was 7·9% (SD 1·1), mean duration of diabetes was 2·5 years (SD 4·4), and mean BMI was 35·8 kg/m2 (SD 7·0). 490 (91%) participants completed the treatment period on study drug and 504 (94%) completed the study. For the treatment regimen estimand, the mean change from baseline in HbA1c concentration was -1·69% (SE 0·11) with retatrutide 4 mg, -1·86% (0·10) with 9 mg, and -1·94% (0·08) with 12 mg, versus -0·81% (0·12) with placebo, resulting in estimated treatment differences versus placebo of -0·88% (95% CI -1·18 to -0·59) with retatrutide 4 mg, -1·04% (-1·32 to -0·76) with 9 mg, and -1·12% (-1·39 to -0·85) with 12 mg (all p<0·0001). The mean percentage change from baseline in bodyweight was -11·5% (SE 0·7) with retatrutide 4 mg, -13·9% (0·8) with 9 mg, and -15·3% (0·8) with 12 mg, versus -2·6% (0·5) with placebo. The most frequent adverse events with retatrutide were generally mild to moderate gastrointestinal events, which subsided over time. Study intervention discontinuations due to adverse events were 2-5% with retatrutide and 0% with placebo. No severe hypoglycaemia was reported. Two deaths occurred during the study, both in the retatrutide 4 mg group and unrelated to the study drug. INTERPRETATION: Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes. FUNDING: Eli Lilly and Company. Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. DOI: 10.1016/S0140-6736(26)0096

Mentions Retatrutide

Central fractalkine-CX3CR1 signaling mediates systemic LPS-induced inhibition of LH pulses in female rats.

1. Endocrinology. 2026 Jun 3:bqag067. doi: 10.1210/endocr/bqag067. Online ahead of print. Central fractalkine-CX3CR1 signaling mediates systemic LPS-induced inhibition of LH pulses in female rats. Otsuka Y(1), Kadoi S(1), Seki S(1), Yabushita R(1), Ariyoshi R(1), Noda C(1), Hazim S(1), Matsuzaki S(1), Yamada K(1), Uenoyama Y(1), Tsukamura H(1), Inoue N(1). Author information: (1)Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan. Inflammatory diseases often suppress reproductive function in mammals. This study investigated whether central fractalkine-CX3CR1 signaling mediates the inhibition of luteinizing hormone (LH) release induced by intravenous administration of lipopolysaccharide (LPS), an endotoxin, in ovariectomized (OVX) rats treated with diestrous levels of estradiol-17β (E2). Double in situ hybridization (ISH) for the fractalkine gene (Cx3cl1) and fos (a cellular activation marker) revealed that LPS significantly increased the percentage of fos-positive Cx3cl1-expressing cells in the lateral mammillary nucleus (LM) and the number of Cx3cl1-expressing cells in the paraventricular nucleus (PVN). Central administration of AZD8797, an CX3CR1 antagonist significantly restored LPS-induced decreases in the mean LH concentrations and the amplitude and baseline of LH pulses. Furthermore, LPS administration significantly increased the percentage of fos-positive fractalkine receptor gene (Cx3cr1)-expressing cells in the arcuate nucleus (ARC), whereas AZD8797 treatment significantly attenuated this LPS-induced increase. ISH for Cx3cr1 and Iba1 (a microglial marker) immunohistochemistry revealed that most Cx3cr1-expressing cells were Iba1-positive. Additionally, Cx3cr1-positive signals were observed adjacent to kisspeptin gene (Kiss1)-expressing cells in the ARC, although a few ARC Kiss1-expressing cells also exhibited Cx3cr1 expression. Collectively, these findings demonstrate that central fractalkine-CX3CR1 signaling, at least in part, mediates the suppression of LH pulses induced by systemic LPS. LM and PVN fractalkine neurons might suppress ARC kisspeptin neurons-the center for gonadotropin-releasing hormone/LH pulse generation-via neighboring CX3CR1-expressing microglial cells. These findings may contribute to the development of therapeutic strategies to mitigate inflammation-associated reproductive dysfunction in both livestock and humans. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. DOI: 10.1210/endocr/bqag067 PMID: 42236284

Mentions Kisspeptin

Dynamic modulation of LH secretion by continuous kisspeptin infusion in healthy men.

1. Hormones (Athens). 2026 Jun 2. doi: 10.1007/s42000-026-00795-y. Online ahead of print. Dynamic modulation of LH secretion by continuous kisspeptin infusion in healthy men. Naveed A(1), Lippincott MF(1), Stamou M(1), Balasubramanian R(1), Bryant NK(1), Seminara SB(2). Author information: (1)Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. (2)Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. sseminara@mgh.harvard.edu. PURPOSE: Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) release and, by extension, gonadotropin secretion. Although continuous kisspeptin administration has been shown to dampen kisspeptin-induced GnRH release in non-human primates [1, 2], this has not been replicated in the limited human studies reported to date. The objective of this study was to examine the effects of continuous kisspeptin administration on luteinizing hormone (LH) secretion in healthy men. METHODS: Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 h and underwent frequent blood sampling to characterize the effect on reproductive hormones. RESULTS: Continuous administration of kisspeptin resulted in an immediate increase in LH concentrations, from a baseline of 2.8-3.8 mIU/mL to the highest values of 17.5-30.6 mIU/mL (5- to eightfold above baseline), reached within 12-20 h of infusion onset. LH concentrations subsequently declined by 13-47% from max to end of the infusion, settling at 10.7-22.8 mIU/mL. FSH and testosterone rose modestly in parallel. CONCLUSION: While kisspeptin boluses have been employed to probe GnRH pulse generation, continuous infusion of kisspeptin is a complementary physiologic tool used to study dynamic changes in GnRH-induced LH secretion. Further studies are warranted to further elucidate the physiologic response of the kisspeptin receptor to non-pulsatile ligand administration. CLINICAL TRIAL REGISTRATION: NCT01438073 (August 24, 2011). © 2026. The Author(s). DOI: 10.1007/s42000-026-00795-y PMID: 42230485 Conflict of interest statement: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Mass General Brigham Institutional Review Boards (IRB). Consent: Informed consent was obtained from all individual participants included in the study. Competing interests: Stephanie Seminara has a financial interest in SeNa Therapeutics, which is developing treatments for reproductive disorders. Dr. Seminara’s interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict of interest policies. The other authors have nothing to disclose.

Mentions Kisspeptin

A Hydrophobic Tag-Assisted Liquid-Phase Strategy for the Synthesis of Retatrutide.

1. Org Lett. 2026 Jun 1. doi: 10.1021/acs.orglett.6c02001. Online ahead of print. A Hydrophobic Tag-Assisted Liquid-Phase Strategy for the Synthesis of Retatrutide. Mao CY(1), Pang ZJ(1), Qiao GY(1), Dong L(1). Author information: (1)Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Retatrutide is a novel triple agonist that targets the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R). At present, its synthesis relies predominantly on solid-phase peptide synthesis (SPPS), an approach that suffers from inherent limitations in terms of efficiency, scalability, and structural flexibility. In this study, we present a novel method for the synthesis of Retatrutide, namely hydrophobic tag-assisted liquid-phase peptide synthesis (LPPS). This method provides a practical and flexible alternative to conventional SPPS for the synthesis of Retatrutide. DOI: 10.1021/acs.orglett.6c02001 PMID: 42224238

Mentions Retatrutide

KNDy kisspeptin is required for metabolic homeostasis in female mice in an ovarian hormone-independent manner.

1. J Neuroendocrinol. 2026 Jun;38(6):e70208. doi: 10.1111/jne.70208. KNDy kisspeptin is required for metabolic homeostasis in female mice in an ovarian hormone-independent manner. Nandankar N(1)(2), Negrón AL(3), Ganesh H(1)(4), Youssef N(1), Farooq S(1)(2), Al-Samerria S(3), Levine JE(5)(6), Radovick S(3). Author information: (1)Department of Pediatrics, Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA. (2)Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA. (3)Department of Pediatrics, University of Arizona College of Medicine, Phoenix, Arizona, USA. (4)Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA. (5)Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. (6)Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA. Disorders of gonadotropin pulsatility contribute to reproductive dysfunction in humans and are often associated with metabolic dysfunction. Hypogonadotropic hypogonadism is characterized by chronically insufficient gonadotropin hormone production, leading to reproductive and metabolic impairments, such as infertility and obesity. Polycystic ovary syndrome (PCOS) is characterized by accelerated gonadotropin hormone production leading to reproductive and metabolic deficits, including oligomenorrhea, infertility, and an increased risk of type 2 diabetes mellitus. Hypothalamic kisspeptin is a key regulator of gonadotropin secretion, and disruptions in kisspeptin signaling result in abnormal gonadotropin pulsatility. Emerging evidence also implicates kisspeptin in energy metabolism. This study investigates the neuroendocrine mechanisms by which kisspeptin within KNDy neurons influences metabolic homeostasis. Using a Pdyn-Cre/Kiss1fl/fl knock-out (Kiss1Pdyn KO) mouse model, we combined diet-induced obesity, metabolic testing, and ovarian hormone depletion to assess the role of KNDy neuron kisspeptin in metabolic regulation and the interaction with sex steroids. Peripheral metabolism was more severely impacted in Kiss1Pdyn KO females than in KO males, with greater reproductive deficits observed in females. Abnormal glucose metabolism was partly attributable to the lack of ovarian steroids. Our findings indicate that loss of KNDy neuron kisspeptin in females promotes obesity through reduced energy expenditure without altering feeding behavior. Furthermore, this study identifies a female-biased role for KNDy kisspeptin as a central integrator of reproductive and metabolic signals. © 2026 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology. DOI: 10.1111/jne.70208 PMID: 42219677 [Indexed for MEDLINE]

Mentions Kisspeptin

Forword for efficacy and safety of tirzepatide in patients with heart failure with preserved ejection fraction: A systematic review and meta-analysis.

1. Dis Mon. 2026 Jun;72(6):102098. doi: 10.1016/j.disamonth.2026.102098. Epub 2026 Mar 20. Forword for efficacy and safety of tirzepatide in patients with heart failure with preserved ejection fraction: A systematic review and meta-analysis. Leikin JB(1). Author information: (1)Division of Environmental and Occupational Health Sciences and the Occupational and Environmental Medicine Service of UI Health at the University of Illinois at Chicago Editor-in-Chief: Disease-a-Month, United States. Electronic address: jerroldleikin@gmail.com. DOI: 10.1016/j.disamonth.2026.102098 PMID: 41862385

Mentions Tirzepatide

Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells.

1. Cytotechnology. 2026 Jun;78(3):98. doi: 10.1007/s10616-026-00967-z. Epub 2026 Apr 28. Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells. Lee JY(1), Lee J(2), Jung WK(3), Je JY(1), Lee SJ(1)(4). Author information: (1)Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan, 48513 Republic of Korea. (2)Department of Pathology, School of Medicine, University of California San Diego, CA La Jolla, USA. (3)Major of Biomedical Engineering, Division of Smart Healthcare, Pukyong National University, Busan, 48513 Republic of Korea. (4)Major of Human Bio-convergence, Pukyong National University, 45 Yongso-ro, Information Technology and Convergence Building, Room 414, Busan, 48513 Republic of Korea. Hepatocellular steatosis, an early stage within the non-alcoholic fatty liver disease (NAFLD) spectrum, is characterized by excessive lipid accumulation and oxidative stress in hepatocytes. This study examined the protective role of Lysine-Proline-Valine (KPV), an endogenous tripeptide derived from α-melanocyte-stimulating hormone, against oleic acid (OA)-induced oxidative damage and lipid accumulation in hepatic epithelial HepG2 cells. OA treatment markedly enhanced hepatic lipid deposition by upregulation of fatty acid synthase (FAS) expression. Treatment with KPV (100 µg/mL) significantly attenuated OA-induced lipid accumulation and suppressed FAS expression without inducing cytotoxicity. Mechanistic analysis revealed that KPV reduced reactive oxygen species generation, thereby preventing activation of extracellular signal-regulated kinase. KPV also downregulated AKT phosphorylation, leading to inhibition of mTORC1 phosphorylation under hepatic steatosis conditions. Furthermore, KPV regulated the phosphorylation of peroxisome proliferator-activated receptor gamma, a key transcription factor in de novo lipogenesis, thereby normalizing FAS expression. These findings suggest that KPV acts as an effective antioxidant regulator of lipogenic signaling and may hold potential as a therapeutic candidate for attenuating hepatocellular steatosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-00967-z. © The Author(s), under exclusive licence to Springer Nature B.V. 2026. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. DOI: 10.1007/s10616-026-00967-z PMCID: PMC13125694 PMID: 42064835 Conflict of interest statement: Competing interestsThe authors declare no competing interests.

Mentions KPV

Childhood obesity and cardiac risk in youth: Emerging challenges toward 2050.

1. Clin Nutr ESPEN. 2026 Jun;73:103260. doi: 10.1016/j.clnesp.2026.103260. Epub 2026 Mar 31. Childhood obesity and cardiac risk in youth: Emerging challenges toward 2050. Mishra NK(1). Author information: (1)College of Pharmaceutical Sciences, Puri (Affiliated to Odisha University of Health Sciences, Bhubaneswar), Baliguali, Puri-konark Marine Drive Road, Puri, Odisha, 752004, India. Electronic address: montu.mph@gmail.com. Pediatric obesity is increasing at an alarming rate, affecting over 381 million children worldwide and emerging as a critical public health issue. According to World Health Organization (WHO) 2016, 40% of adults are overweight and 13% are obese, highlighting obesity's persistence throughout life. Childhood obesity significantly heightens the risk of adult obesity and cardiovascular diseases (CVD) such as atherosclerosis and coronary artery disease, potentially leading to a global health crisis by 2050. Genetic predispositions identified through genome-wide association studies (GWAS) contribute to elevated body mass index (BMI), yet lifestyle factors reduced physical activity, prolonged screen time, and consumption of high-calorie, low-nutrient foods remain key drivers. This study aim is to explore the Real-world data (RWD) on childhood obesity from major countries, prevalence, risk factors, and cardiovascular consequences of pediatric obesity, evaluating public health initiatives, lifestyle interventions, and therapeutic strategies to address this growing concern. Data collected from PubMed, Scopus, and Springer databases reveal that childhood obesity is closely linked to hypertension, dysglycemia, dyslipidemia, and other cardiovascular disorders (heart attack, arrhythmias and stroke). The WHO Global Action Plan on Physical Activity 2018-2030 (GAPPA) emphasizes urgent preventive measures. Current management strategies include lifestyle modification, pharmacotherapy, and bariatric surgery. Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and liraglutide are effective for weight management but commonly cause gastrointestinal adverse effects. The SURMOUNT-5 trial demonstrated superior weight-loss outcomes with tirzepatide, with a similar gastrointestinal safety profile. Emerging therapies including cagrilintide plus semaglutide, oral agents such as orforglipron and danuglipron, and the triagonist retatrutide may improve adherence and accessibility; however, these agents remain investigational and are currently under clinical evaluation. Despite promising advancements, gene therapy for pediatric obesity remains in the experimental phase. Overall, addressing childhood obesity requires multifaceted interventions combining public health initiatives, behavioral changes, and novel therapeutic strategies to mitigate cardiovascular risks and promote sustainable health outcomes. Copyright © 2026 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.clnesp.2026.103260 PMID: 41933725 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Retatrutide

Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide.

1. Clin Pharmacokinet. 2026 Jun 1. doi: 10.1007/s40262-026-01654-0. Online ahead of print. Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide. Nielsen MJF(1), Becker NP(2)(3), Duus HHH(2), Kirkeby K(2), Kupčová V(4), Lauenborg BW(2), Low B(2), Svolgaard O(2), Witten L(2). Author information: (1)Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark. MJXF@novonordisk.com. (2)Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark. (3)F. Hoffmann-La Roche Ltd., Grenzacherstrasse, Basel, Switzerland. (4)Medical Faculty, Dérer's Hospital, Bratislava, Slovakia. BACKGROUND AND OBJECTIVES: Cagrilintide is a long-acting amylin agonist under development as monotherapy for weight management and as a fixed-dose combination with the glucagon-like peptide-1 receptor agonist semaglutide (CagriSema) for weight management and treatment of type 2 diabetes. Two studies were conducted to assess the effects of renal or hepatic impairment on pharmacokinetics, safety and tolerability following single doses of cagrilintide. METHODS: In both studies, adult participants were categorised into four groups on the basis of renal or hepatic function (normal function and mild, moderate or severe impairment) and received a single dose of cagrilintide 0.6 or 0.9 mg, respectively. The primary endpoint was area under the cagrilintide plasma concentration curve from time zero extrapolated to infinity (AUC0-∞) from baseline (day 1) to day 36 (renal impairment study) or day 39 (hepatic impairment study). Other pharmacokinetic parameters included maximum observed cagrilintide plasma concentration (Cmax), time to Cmax (tmax) and safety. RESULTS: The renal impairment study included 33 participants (normal function, n = 14; mild impairment, n = 7; moderate impairment, n = 7; severe impairment, n = 5) and the hepatic impairment study included 32 participants (normal function, n = 14; mild impairment, n = 7; moderate impairment, n = 7; severe impairment, n = 4). In both studies, total cagrilintide exposure (AUC0-∞), Cmax and other pharmacokinetic parameters were similar across groups with no consistent patterns observed with renal or hepatic impairment. Compared with normal renal function, the estimated ratio of the mean AUC0-∞ was 1.23 (90% confidence interval [CI], 0.91-1.66) in mild impairment, 1.18 (0.87-1.59) in moderate impairment and 1.21 (0.87-1.68) in severe impairment. Compared with normal hepatic function, the estimated ratio of the mean AUC0-∞ was 0.99 (0.89-1.11) in mild impairment, 1.01 (0.91-1.12) in moderate impairment and 1.11 (0.96-1.30) in severe impairment. Overall, 21 and 16 treatment-emergent adverse events (TEAEs) were reported in 11 and 9 participants in the renal and hepatic studies, respectively. In both studies, no serious TEAEs, TEAEs leading to study withdrawal or deaths were reported. No increase in number of adverse events with increasing renal or hepatic impairment was observed, and no new safety or tolerability findings with cagrilintide were identified with renal or hepatic impairment. CONCLUSIONS: In these studies, within the limitations of small sample sizes, no clinically relevant differences in cagrilintide pharmacokinetics were observed in participants with renal or hepatic impairment compared with those with normal function, suggesting that dose adjustment is not warranted for these populations. Cagrilintide was well-tolerated and there were no unexpected safety issues. TRIAL REGISTRATION: Studies are registered at ClinicalTrials.gov (NCT04209049 registered 23 December 2019 and NCT05564104 registered 3 October 2022). © 2026. The Author(s). DOI: 10.1007/s40262-026-01654-0 PMID: 42228334 Conflict of interest statement: Declarations. Conflict of interest: Mette JF Nielsen, Helene H Hansen Duus, Katrine Kirkeby, Britt W Lauenborg, Benjamin Low and Louise Witten are employees and stockholders of Novo Nordisk A/S. Niels

Mentions CagriSema

Do GLP-1 Receptor Agonists Sabotage Fat Grafts? : A Scoping Review of GLP-1 Receptor Agonist Effects on Adipocyte Biology and Implications for Autologous Fat Transfer.

1. Aesthet Surg J. 2026 Jun 1:sjag108. doi: 10.1093/asj/sjag108. Online ahead of print. Do GLP-1 Receptor Agonists Sabotage Fat Grafts? : A Scoping Review of GLP-1 Receptor Agonist Effects on Adipocyte Biology and Implications for Autologous Fat Transfer. Chalhoub X(1), Yang Ng Z(2). Author information: (1)Department of Plastic Surgery, Imperial College Healthcare NHS Trust, Plastic Surgery, London, UK. (2)Plastic surgery consultant in private practice in Singapore. The rapid adoption of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has created an unprecedented overlap with aesthetic surgery. Millions of patients experiencing GLP-1-mediated weight loss now present with facial volume depletion, soft tissue deflation, and contour irregularities; conditions for which autologous fat grafting remains the gold-standard solution. However, the fundamental biology of GLP-1 receptor agonism may be inherently antagonistic to the mechanisms upon which fat graft survival depends. This scoping review, conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR), synthesizes current preclinical and clinical evidence on the effects of semaglutide, liraglutide, tirzepatide, and the emerging triple agonist retatrutide on adipocyte metabolism, adipose-derived stem cell (ASC) function, and tissue revascularization, and maps these effects onto established models of fat graft take. We identify multiple potential interference points, including GLP-1-mediated adipocyte browning and thermogenic activation with upregulation of UCP1 and mitochondrial uncoupling, enhanced lipolysis through ATGL and HSL upregulation, suppression of white adipogenic differentiation in ASCs with preferential commitment toward thermogenic beige lineages, and modulation of inflammatory and angiogenic signaling during the critical revascularization window. The growing off-label use of retatrutide in bodybuilding communities introduces additional concerns through glucagon receptor-mediated lipolysis and thermogenesis. Despite the strong mechanistic rationale, no clinical or preclinical studies have directly examined fat graft outcomes in patients receiving incretin-based therapies. We propose a framework for future investigation and offer preliminary, mechanism-based clinical considerations regarding perioperative GLP-1 RA management in fat transfer patients. These recommendations should be understood as hypothesis-generating rather than evidence-based guidelines. © The Author(s) 2026. Published by Oxford University Press on behalf of The Aesthetic Society. DOI: 10.1093/asj/sjag108 PMID: 42219269

Mentions Retatrutide

BPC-157 and Its Novel Hybrid Analogs as Inhibitors of Acetylcholinesterase.

1. Int J Mol Sci. 2026 May 30;27(11):4984. doi: 10.3390/ijms27114984. BPC-157 and Its Novel Hybrid Analogs as Inhibitors of Acetylcholinesterase. Jelińska J(1), Józwiak M(2), Szeleszczuk Ł(3), Sikora K(4), Kamysz W(4), Kleczkowska P(5), Gackowski M(6), Grodner B(1). Author information: (1)Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland. (2)Maria Skłodowska-Curie Medical Academy in Warsaw, al. Solidarności 12, 03-411 Warsaw, Poland. (3)Department of Organic and Physical Chemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland. (4)Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland. (5)Department of Nursing and Other Health Professions, Center of Postgraduate Medical Education, 01-826 Warsaw, Poland. (6)Department of Toxicology and Bromatology, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 2 Jurasza Str., 85-089 Bydgoszcz, Poland. Acetylcholinesterase (AChE) inhibition remains a key therapeutic strategy in the management of neurodegenerative disorders such as Alzheimer's disease. In this study, the inhibitory potential of the gastric pentadecapeptide BPC-157 and two newly designed hybrid analogs, CIARA-1 and CIARA-2, was investigated for the first time. The hybrid peptides were rationally designed by combining a BPC-157-derived fragment with an arginine-containing C-terminal sequence to enhance interactions with the enzyme's active and peripheral binding sites. Enzyme kinetics were evaluated using a modified Ellman assay, and inhibition parameters were determined through Lineweaver-Burk analysis. All tested compounds exhibited a competitive mechanism of inhibition, as evidenced by increased Michaelis-Menten constant (Km) values with unchanged maximum velocity (Vmax), indicating competition with the substrate at the catalytic site of AChE. Among the tested compounds, CIARA-1 demonstrated the highest inhibitory potency, reflected by the lowest inhibition constant (Ki = 0.24 mM) and IC50 value (2.52 mM), followed by CIARA-2 (Ki = 0.29 mM; IC50 = 2.73 mM) and BPC-157 (Ki = 0.48 mM; IC50 = 2.80 mM). These findings were consistent with molecular modeling predictions, supporting stronger binding interactions for CIARA-1. Despite significantly lower potency compared to clinically used AChE inhibitors, the studied peptides represent a promising scaffold for further optimization. Overall, this work demonstrates that BPC-157 and its hybrid analogs act as reversible competitive AChE inhibitors, with enhanced activity observed for structurally modified derivatives. The results highlight the potential of peptide-based hybrid molecules as multifunctional candidates in the development of novel therapeutics targeting cholinergic dysfunction. DOI: 10.3390/ijms27114984 PMCID: PMC13257072 PMID: 42278509 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions BPC-157

Prolonged Dysesthesia After Massive Accidental Semaglutide Overdose: A Case Report.

1. J Am Coll Emerg Physicians Open. 2026 May 29;7(4):100427. doi: 10.1016/j.acepjo.2026.100427. eCollection 2026 Aug. Prolonged Dysesthesia After Massive Accidental Semaglutide Overdose: A Case Report. Quarenghi M(1), Stanga A(1), Bergamaschi A(1). Author information: (1)Clinical Nutrition and Dietetics, Department of Internal Medicine, Ospedale San Giovanni, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland. The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has expanded rapidly worldwide for the treatment of obesity, accompanied by a parallel increase in medication errors and accidental overdoses. Gastrointestinal symptoms are the most commonly reported adverse effects in cases of supratherapeutic exposure, whereas neurologic manifestations remain poorly characterized. We report a case of a 50-year-old man with obesity receiving weekly semaglutide 2.4 mg who accidentally administered a total dose of 9.6 mg due to a pen-device handling error. Two days after the injection, he developed generalized burning dysesthesia and marked asthenia in the absence of nausea, vomiting, or abdominal pain. Laboratory tests performed 4 days after exposure were unremarkable. Symptoms gradually improved and resolved completely within 7 days without specific treatment. Clinical trial data suggest a possible dose-related signal for dysesthesia with high-dose oral semaglutide; however, reports of acute parenteral supratherapeutic exposure presenting with isolated neurologic symptoms are scarce. This case suggests that isolated dysesthesia may occur following semaglutide overdose and may follow a benign, self-limited course, a presentation relevant to emergency physicians given the increasing use of GLP-1 RAs. © 2026 The Author(s). DOI: 10.1016/j.acepjo.2026.100427 PMCID: PMC13241993 PMID: 42256775 Conflict of interest statement: All authors have affirmed they have no conflicts of interest to declare.

Mentions Semaglutide

Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury.

1. Sci Rep. 2026 May 28. doi: 10.1038/s41598-026-55449-1. Online ahead of print. Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury. Yıldırım AK(1), Demirtaş H(2), Özer A(2), Arslan M(3)(4)(5). Author information: (1)Health Sciences University Gulhane Training and Research Hospital, Ankara, Turkey. (2)Department of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey. (3)Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey. mustarslan@gmail.com. (4)Application and Research Centre for Life Sciences, Gazi University, Ankara, Turkey. mustarslan@gmail.com. (5)Centre for Laboratory Animal Breeding and Experimental Research (GÜDAM), Gazi University, Ankara, Turkey. mustarslan@gmail.com. Ischemia-reperfusion (I/R) injury remains a major complication in peripheral arterial disease, characterized by oxidative stress, inflammation, and apoptosis. Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, has demonstrated cytoprotective properties in multiple tissues. This study aimed to evaluate the protective effects of BPC 157 in a rat model of lower limb I/R injury. Twenty-four male Wistar albino rats were randomized into four groups (n = 6): SHAM, B (BPC 157 only), IR (I/R), and IRB (I/R + BPC 157). I/R was induced by abdominal aortic clamping for 45 min followed by 2 h of reperfusion. BPC 157 (20 µg/kg, intraperitoneal) was administered at the 45th minute of ischemia in B and IRB groups. Biochemical markers (MDA, SOD, TAS, TOS) were measured in serum. Gene expression of Il-6, Hif-1α, p53, Bcl-2, Bax, and Casp3 was assessed by qRT-PCR, while immunohistochemistry evaluated VEGF, eNOS, IL-6, and Caspase-3 expression. Histopathological changes were scored with hematoxylin-eosin and Masson's trichrome staining. I/R significantly increased MDA, TOS, p53, Bax, Casp3, Hif-1α, Il-6, and histopathological injury scores, while reducing SOD, TAS, and VEGF expression. Bcl-2 mRNA was not significantly reduced by I/R compared with SHAM; however, BPC 157 significantly increased Bcl-2 expression compared with IR. In the IRB group, BPC 157 reduced MDA and TOS, restored SOD and TAS, downregulated p53, Bax, and Casp3, reduced IL-6 and Caspase-3 immunoreactivity, and partially restored VEGF expression. Histological analysis confirmed improved muscle architecture and reduced collagen deposition in IRB compared with IR. BPC 157 appears to exert protective effects against skeletal muscle I/R injury by attenuating oxidative stress, modulating apoptosis, reducing inflammation, and supporting angiogenic activity. These findings suggest that BPC 157 may represent a potential therapeutic candidate for mitigating reperfusion injury; however, further studies with larger cohorts and dose-response evaluations are required to confirm these effects and establish clinical relevance. © 2026. The Author(s). DOI: 10.1038/s41598-026-55449-1 PMID: 42204242 Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests. Institutional Review Board Statement: Ethical approval for the study was obtained from the Gazi University Animal Experiments Local Ethics Committee (Ankara, Turkey; Approval number: G.Ü.ET-24.049, date: 27.05.2024). All methods were performed in accordance with relevant institutional and international guidelines and regulations, including the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, 1986) and the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals (2020). The study was conducted and reported in accordance with the ARRIVE guidelines.

Mentions BPC-157

Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs.

1. Res Sq [Preprint]. 2026 May 26:rs.3.rs-9520102. doi: 10.21203/rs.3.rs-9520102/v1. Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs. Mazzola J, Rosenfeld M, Tucker M, Wezeman J, Ladiges W, Liao G. Age-related cognitive decline (ARCD) is driven by conserved biological mechanisms of aging, yet no gerotherapeutic directly targets these processes in the brain. Glycyl-L-histidyl-L-lysine complexed with copper (GHK-Cu) is an endogenous peptide with regenerative and anti-inflammatory properties that declines with age. Whether its effects on cognitive aging depend on delivery route or exposure duration remains unclear. Aged C57BL/6J mice (20-21 months) received GHK-Cu (15 mg/kg) via short-term intraperitoneal (IP; 5 days) or longer-term intranasal (IN; 8 weeks) administration. Hippocampal-dependent escape learning was assessed using a spatial navigation task. Molecular effects were evaluated using hippocampal immunohistochemistry and bulk RNA sequencing. Differential gene expression was analyzed using DESeq2 with false discovery rate (FDR) correction, and pathway-level changes were assessed via gene set enrichment analysis (GSEA). IN GHK-Cu improved escape latency across Trials 2-4 in both sexes ( P  < 0.05), whereas IP dosing produced a transient improvement in males during Trial 2 ( P  < 0.05) without sustained effects or improvement in females. IN treatment increased synaptophysin in females ( P  < 0.001) and decreased GFAP in both sexes ( P  < 0.01), while IP treatment reduced TGF-β, GFAP, and MCP-1 in males ( P  < 0.05) and decreased p21 in females ( P  < 0.0001). Transcriptomic analysis revealed distinct molecular programs. IN GHK-Cu induced coordinated suppression of oxidative phosphorylation (male NES - 5.44, female NES - 4.20; FDR < 0.0001) and MYC target pathways (female NES - 4.31, FDR < 0.0001), with additional attenuation of PI3K-AKT-mTOR signaling in females (NES - 3.15, FDR = 0.062). In contrast, IP treatment activated oxidative phosphorylation (female NES 4.97, FDR < 0.001), DNA repair (NES 5.58, FDR < 0.001), and MYC targets (NES 4.34, FDR = 0.002), indicating engagement of acute stress-response and repair pathways. GHK-Cu improves hippocampal-dependent learning in aged mice through distinct biological modes: IP exposure activates repair and stress-response pathways, whereas IN delivery induces sustained suppression of growth and mitochondrial metabolic signaling associated with aging biology. These findings demonstrate that functional cognitive improvement can arise from divergent molecular states and identify administrative route and exposure duration as key determinants of gerotherapeutic response. DOI: 10.21203/rs.3.rs-9520102/v1 PMCID: PMC13232416 PMID: 42245779

Mentions GHK-Cu

Orforglipron (Foundayo) - a second oral GLP-1 receptor agonist for weight loss.

1. Med Lett Drugs Ther. 2026 May 25;68(1755):81-83. doi: 10.58347/tml.2026.1755a. Orforglipron (Foundayo) - a second oral GLP-1 receptor agonist for weight loss. [No authors listed] DOI: 10.58347/tml.2026.1755a PMID: 42139026

Mentions Orforglipron

Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review.

1. Eur J Clin Pharmacol. 2026 May 22;82(6):154. doi: 10.1007/s00228-026-04079-7. Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review. Laroche ML(1)(2), Géniaux H(3), Jardou M(3). Author information: (1)Regional Center of Pharmacovigilance, Department of Pharmacology, Toxicology and Pharmacovigilance, Limoges' University Hospital, Limoges, France. marie-laure.laroche@unilim.fr. (2)Faculty of Medicine, Department of Pharmacology, University of Limoges, 2 avenue Dr Marcland, Limoges, 87000 LIMOGES Cedex, France. marie-laure.laroche@unilim.fr. (3)Regional Center of Pharmacovigilance, Department of Pharmacology, Toxicology and Pharmacovigilance, Limoges' University Hospital, Limoges, France. PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) agonists. We performed a pharmacovigilance data-mining analysis to characterise cases of dysesthesia related to GLP-1R. METHODS: We conducted a disproportionality analysis using VigiBase data on GLP-1R (Anatomical Therapeutic Chemical classification: ATC code A10BJ) and tirzepatide, focusing on the HLT (High Level Term) "Paraesthesia and dysesthesia", with the Information Component (IC). Additionally, we reviewed all narratives of dysesthesia cases in the French Pharmacovigilance database to extract clinical and pharmacological characteristics. A literature review complemented this analysis. RESULTS: Exenatide was significantly associated with hypoesthesia or oral paraesthesia, semaglutide and tirzepatide with hyperaesthesia, and semaglutide with dysesthesia and burning sensation. Dysesthesia appears to be dose-dependent, occurring more frequently at higher doses and with more potent GLP-1R, whether used for weight management or type 2 diabetes. Discontinuation was often performed, followed by spontaneous favourable outcomes, and cases of rechallenge were observed. Skin burning sensations represent a distinctive form of dysesthesia. CONCLUSION: Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide. © 2026. The Author(s). DOI: 10.1007/s00228-026-04079-7 PMCID: PMC13194321 PMID: 42168638 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to Participate: This study, based on anonymized pharmacovigilance data and a literature review, is exempt from formal review by the Limoges University Hospital Institutional Review Board. The requirement for written informed consent was waived owing to the use of a population-level dataset. Competing interests: The authors declare no competing interests.

Mentions Retatrutide

DES-mediated self-assembled polypeptides: Synergistic neuromuscular signaling inhibition for anti-aging.

Mentions Argireline

Injectable Peptides in Sports Medicine: A Structured Narrative Review of Evidence, Safety, and Antidoping Implications.

1. JBJS Rev. 2026 May 20;14(5). doi: 10.2106/JBJS.RVW.26.00027. eCollection 2026 May 1. Injectable Peptides in Sports Medicine: A Structured Narrative Review of Evidence, Safety, and Antidoping Implications. Villegas Meza AD(1), Nocek M(1), Mitchell BC(1)(2), Lizarraga M(3), DeFoor MT(1)(2), Ruzbarsky JJ(1)(2), Huard J(1), Philippon MJ(1)(2). Author information: (1)The Steadman Philippon Research Institute, Vail, Colorado. (2)The Steadman Clinic, Vail, Colorado. (3)University of California, San Francisco School of Medicine, San Francisco, California. BACKGROUND: Injectable peptides are increasingly promoted for musculoskeletal recovery, tissue repair, and performance enhancements; however, clinical adoption has outpaced high-quality evidence and regulatory consensus. PURPOSE: To summarize contemporary human and translational evidence (January 1, 2020-August 31, 2025) for injectable peptides relevant to orthopaedics and sports medicine, and to clarify safety, product quality, regulatory, antidoping implications, and clinical outcomes. STUDY DESIGN: Structured narrative review. METHODS: PubMed/MEDLINE, Embase, and Web of Science were searched (January 1, 2020-August 31, 2025). Eligible studies included randomized controlled trials, prospective human studies, and translational investigations directly applicable to musculoskeletal care; noninjectable formulations and nonmusculoskeletal indications were excluded. Results were synthesized qualitatively; risk of bias for human trials was appraised using standard tools. RESULTS: Five functional peptide classes were identified. Glucagon-like peptide-1 receptor agonists (e.g., semaglutide) are the only class supported by reproducible randomized evidence of symptomatic improvement in knee osteoarthritis, with benefits primarily mediated by clinically meaningful weight loss and putative anti-inflammatory effects, whereas structural cartilage modification remains unproven. Collagen-derived injectable preparations show preliminary postoperative symptom/early recovery benefits in small, single-center prospective human studies. Regenerative peptides (e.g., body protection compound-157 and thymosin derivatives) and growth hormone axis secretagogues (e.g., CJC-1295, ipamorelin, and tesamorelin) remain investigational, with uncertain safety profiles, product quality concerns, and widespread antidoping restrictions. CONCLUSIONS: Injectable peptides for sports medicine remain largely experimental. Clinical use should be confined to approved metabolic agents for indicated conditions and to rigorously designed research protocols. Clinicians caring for athletes must counsel patients regarding uncertain efficacy, product quality, safety risks, and antidoping implications. LEVEL OF EVIDENCE: Level V. See Instructions for Authors for a complete description of levels of evidence. STRENGTH OF RECOMMENDATION TAXONOMY: Predominantly C. Copyright © 2026 by The Journal of Bone and Joint Surgery, Incorporated. DOI: 10.2106/JBJS.RVW.26.00027 PMID: 42160466 [Indexed for MEDLINE] Conflict of interest statement: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B330).

Mentions Tesamorelin

Cagrilintide and CagriSema for weight reduction and metabolic risk modification in overweight or obesity: a systematic review and meta-analysis.

1. J Diabetes Metab Disord. 2026 May 20;25(1):140. doi: 10.1007/s40200-026-01942-3. eCollection 2026 Jun. Cagrilintide and CagriSema for weight reduction and metabolic risk modification in overweight or obesity: a systematic review and meta-analysis. Rao H(1), Kumar S(1), Ali SME(2), Asif HM(1), Kumar M(1), Kumar L(1), Raja A(1). Author information: (1)Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan. (2)Department of Medicine, Abbasi Shaheed Hospital, Karachi, Pakistan. BACKGROUND: Obesity is a global health challenge associated with substantial cardiometabolic morbidity. Cagrilintide, a long-acting amylin analogue, alone or in combination with semaglutide (CagriSema), has emerged as a novel pharmacologic strategy for weight management. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of cagrilintide-based therapies in adults with overweight or obesity. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted according to PRISMA 2020 and AMSTAR 2. Eligible studies enrolled adults with overweight or obesity randomized to cagrilintide or CagriSema versus placebo and reported at least one efficacy or safety outcome. The primary outcome was percent change in body weight. Secondary outcomes included absolute weight change, waist circumference, blood pressure, glycated hemoglobin (HbA1c), and safety outcomes. Random-effects meta-analyses were conducted, and risk of bias was assessed using the Cochrane RoB 2 tool. RESULTS: Four trials including 5,023 participants were pooled. Cagrilintide significantly reduced percent body weight versus placebo (mean difference - 6.08%, 95% CI - 8.02 to - 4.14), as did CagriSema (- 5.98%, 95% CI - 10.64 to - 1.32). Both interventions significantly reduced absolute body weight. CagriSema produced a significant reduction in waist circumference and HbA1c, whereas cagrilintide alone showed modest blood pressure improvements without significant glycemic effects. Overall adverse events were more frequent with active treatment, but discontinuation rates were comparable to placebo. CONCLUSIONS: Cagrilintide and CagriSema achieved clinically meaningful weight loss with favorable cardiometabolic effects and acceptable tolerability, supporting their role as emerging options in obesity pharmacotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01942-3. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. DOI: 10.1007/s40200-026-01942-3 PMCID: PMC13190888 PMID: 42180166 Conflict of interest statement: Competing interestThe authors declare no competing interests.

Mentions CagriSema

BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers.

1. Pharmaceutics. 2026 May 20;18(5):625. doi: 10.3390/pharmaceutics18050625. BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers. Mateescu DM(1), Gavrilescu DM(2), Constantinescu FE(3), Oancea C(4), Ilie AC(5)(6), Folescu R(7), Popa MD(8), Iurciuc S(9), Muresan CO(10)(11)(12), Enache A(10)(11)(12). Author information: (1)Department of General Medicine, Doctoral School, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (2)Department of Orthodontics, Dental District, Zăgazului 3, One Floreasca Vista, Sector 1, 014261 Bucharest, Romania. (3)Department of Prosthodontics, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, Eroii Sanitari Blvd 8, 050474 Bucharest, Romania. (4)Pulmonology Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania. (5)Department of Public Health and Sanitary Management, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (6)Centre for Translational Research and Systems Medicine, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. (7)Department of Balneology, Medical Recovery and Rheumatology, Family Discipline, Center for Preventive Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (8)Department of Microbiology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (9)Cardiology Department, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (10)Legal Medicine, Timisoara Institute of Legal Medicine, 300041 Timisoara, Romania. (11)Ethics and Human Identification Research Center, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (12)Discipline of Forensic Medicine, Bioethics, Deontology, and Medical Law, Department of Neuroscience, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. Background/Objectives: BPC-157 (body protection compound 157) is a synthetic pentadecapeptide derived from a gastric protein fragment with reported cytoprotective and regenerative properties across multiple organ systems. Despite over three decades of preclinical research demonstrating consistent biological activity, its pharmaceutical development remains rudimentary, with no approved formulation, no validated dosing regimen, and no completed Phase II clinical trial. This review critically evaluates BPC-157 from a biopharmaceutical and drug development perspective, examining its physicochemical and pharmacokinetic properties, formulation challenges across routes of administration, the pharmacokinetic-pharmacodynamic disconnect that characterizes its preclinical profile, and the regulatory and translational barriers that currently preclude clinical advancement. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE, Embase, and Cochrane Library from database inception to April 2026. Search terms included "BPC-157", "BPC157", "body protection compound 157", "pentadecapeptide", and "GEPPPGKPADDAGLV", each combined with "pharmacokinetics", "formulation", "biopharmaceutics", "drug delivery", "clinical trial", "toxicology", and "regulatory". Patent databases (Espacenet, Google Patents) and regulatory agency websites (FDA, EMA, WADA) were searched independently. Searches were supplemented by forward and backward citation tracking of key references. Articles were selected based on relevance to biopharmaceutical characterization, pharmacokinetics, formulation science, clinical evidence, and

Mentions BPC-157

Exosomes Released by Cerebrolysin-Treated Cerebral Endothelial Cells Reverse Fibrin- or tPA-Impaired Endothelial Cell Permeability.

1. Cells. 2026 May 19;15(10):934. doi: 10.3390/cells15100934. Exosomes Released by Cerebrolysin-Treated Cerebral Endothelial Cells Reverse Fibrin- or tPA-Impaired Endothelial Cell Permeability. Teng H(1), Li C(1), Wang M(1), Zhang J(1), Zhang Y(1), Chopp M(1)(2), Zhang ZG(1). Author information: (1)Department of Neurology, Henry Ford Health, Detroit, MI 48202, USA. (2)Department of Physics, Oakland University, Rochester, MI 48309, USA. Cerebrolysin has a salutary effect on impaired cerebral endothelial cell (CEC) permeability. Using an in vitro endothelial permeability assay, the present study tested the hypothesis that exosomes released by Cerebrolysin-treated CECs (Cerebro-Exos) have a robust therapeutic effect on dysfunctional CECs. Stoichiometric analysis showed marked differences in cargo profiles between Cerebro-Exos and exosomes derived from CECs without Cerebrolysin treatment (Naïve-Exos), in which Cerebro-Exos were highly enriched with metabolic and tight junction related proteins compared to Naïve-Exos. Cerebro-Exos had a superior effect compared to Naïve-Exos on restoring CEC integrity impaired by fibrin and tissue plasminogen activator (tPA). Treatment of fibrin- and tPA-challenged CECs with Cerebro-Exos robustly reduced fibrin- and tPA-augmented proteins involved in inflammation and coagulation and substantially increased fibrin- and tPA-decreased proteins that are related to tight junctions and metabolism. Collectively, these data indicate that Cerebro-Exos have a broad effect on improvement of dysfunctional CECs, which is likely achieved by the alteration of CEC proteins. DOI: 10.3390/cells15100934 PMCID: PMC13205112 PMID: 42193943 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mentions Cerebrolysin

Diabetes Mellitus and Stroke: Pathophysiological Connections and Therapeutic Potential of GLP-1 and GLP-1/GIP Receptor Agonists.

1. Pharmaceutics. 2026 May 19;18(5):620. doi: 10.3390/pharmaceutics18050620. Diabetes Mellitus and Stroke: Pathophysiological Connections and Therapeutic Potential of GLP-1 and GLP-1/GIP Receptor Agonists. Paceana MA(1), Tartau LM(2), Boboc IKS(3), Oancea CN(4), Berbecaru-Iovan A(3), Foia CI(2), Tartau CG(2), Bogdan M(3). Author information: (1)Doctoral School, University of Medicine and Pharmacy, 200349 Craiova, Romania. (2)Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania. (3)Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy, 200349 Craiova, Romania. (4)Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania. Both diabetes mellitus (DM) and stroke are major global health challenges with high morbidity and mortality. DM is a major risk factor for stroke, contributing to both increased incidence and worse clinical outcomes. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as well as dual agonists like tirzepatide, have demonstrated significant cardiovascular benefits, raising interest in their potential cerebrovascular effects. This narrative review examines the pathophysiological links between DM and stroke and summarizes recent clinical evidence on the efficacy of GLP-1 RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP RAs) in stroke prevention and management. Current evidence from large cardiovascular outcome trials supports the role of GLP-1 RAs in reducing major adverse cardiovascular events, including stroke, primarily in the context of primary and secondary prevention. Findings suggest that semaglutide and liraglutide may reduce non-fatal stroke incidence, decrease hospitalizations, and improve neurological outcomes in patients with prior stroke. Comparative analyses of major trials suggest that, although stroke reduction may be a class effect of GLP-1 RAs, meaningful differences exist between individual agents, likely due to variations in pharmacokinetics, receptor affinity, and study populations. Additionally, much of the evidence in acute stroke derives from early-phase or ongoing trials, warranting cautious interpretation. Novel therapies, including orforglipron and retatrutide, as well as combinations like Maridebart cafraglutide and CagriSema, may expand future therapeutic options for individuals at high cerebrovascular risk. GLP-1-based therapies show promising neurovascular effects, but large-scale, long-term studies are needed to define their role in post-stroke management and cerebrovascular risk reduction. Overall, GLP-1 RAs should currently be regarded primarily as agents for long-term vascular risk reduction rather than established therapies for acute stroke. While potential neuroprotective effects are emerging, these require confirmation in adequately powered randomized trials. Future studies should aim to identify the patient subgroups most likely to benefit and to determine whether specific agents confer advantages in acute cerebrovascular contexts. A better understanding of the mechanisms underlying potential neuroprotection will be essential to determine whether these therapies can be effectively integrated into stroke management strategies. DOI: 10.3390/pharmaceutics18050620 PMCID: PMC13210960 PMID: 42198313 Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Retatrutide

Orforglipron and the emergence of oral GLP-1 therapy for obesity: efficacy, safety, and clinical positioning.

1. Expert Opin Pharmacother. 2026 May 18:1-12. doi: 10.1080/14656566.2026.2676109. Online ahead of print. Orforglipron and the emergence of oral GLP-1 therapy for obesity: efficacy, safety, and clinical positioning. Zaman W(1), Amin A(1). Author information: (1)Department of Life Sciences, Yeungnam University, Gyeongsan, Republic of Korea. INTRODUCTION: Obesity is a chronic, relapsing disease associated with substantial cardiometabolic morbidity and reduced quality of life. Although pharmacotherapy has advanced rapidly, current treatment options remain limited by tolerability concerns, access barriers, discontinuation, and reluctance toward injectable agents. Orforglipron, a once-daily oral glucagon-like peptide-1 receptor agonist, represents a potentially important step in expanding effective anti-obesity therapy. AREAS COVERED: This review evaluates the emerging role of orforglipron in obesity pharmacotherapy, with emphasis on its mechanistic basis, clinical pharmacology, efficacy, safety, and likely place in therapy. Particular attention is given to its therapeutic rationale as an oral incretin-based agent, evidence supporting clinically meaningful weight reduction, common adverse effects and prescribing considerations, and its potential positioning relative to established oral anti-obesity drugs and injectable incretin therapies. The review also considers treatment sequencing and the practical implications of integrating oral GLP-1 therapy into routine obesity care. EXPERT OPINION: Orforglipron may benefit patients requiring effective weight-management pharmacotherapy who prefer oral treatment. However, its role should be interpreted cautiously: comparative efficacy may not exceed leading injectable incretin therapies, and long-term durability, persistence, affordability, and real-world safety remain uncertain. Its value will depend on route preference, tolerability, access, and individualized treatment goals. DOI: 10.1080/14656566.2026.2676109 PMID: 42138103

Mentions Orforglipron

Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression.

1. Medicina (Kaunas). 2026 May 18;62(5):986. doi: 10.3390/medicina62050986. Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression. Abenavoli L(1)(2), Loricchio AG(1)(2), Lopez I(1)(2), Morano D(1)(2), Ismaiel A(3), Dumitrascu DL(3), Luzza F(1)(2). Author information: (1)Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100 Catanzaro, Italy. (2)Center for Chronic Liver Diseases, "Renato Dulbecco" University Hospital, 88100 Catanzaro, Italy. (3)2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania. Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with metabolic abnormalities, shares pathophysiological pathways with metabolic syndrome, and has become a leading cause of chronic liver disease in industrialized nations. In the absence of approved pharmacological treatments and due to its high risk of progression to advanced fibrosis, MASLD represents a significant clinical challenge. Incretin-based therapies, originally developed for the treatment of type 2 diabetes mellitus and obesity, have recently gained attention as promising therapeutic strategies in hepatology. Among them, GLP-1 receptor agonists have shown efficacy in reducing hepatic steatosis, inflammation, and fibrosis-related biomarkers, primarily through weight loss and enhanced insulin sensitivity. Dual agonists targeting both GLP-1 and GIP receptors, such as tirzepatide, have demonstrated superior outcomes in improving hepatic and metabolic parameters. Emerging agents like cotadutide (a GLP-1/glucagon receptor agonist) and retatrutide (a GLP-1/GIP/glucagon triagonist) represent a novel therapeutic frontier, with early clinical data indicating potent hepatoprotective effects and favorable metabolic remodeling. This narrative review examines the hepatoprotective potential of incretin-based therapies, highlighting how targeted intervention on the underlying metabolic dysfunction may lead to significant improvements in MASLD. These therapies may also exert beneficial effects on fibrosis progression; however, the currently available evidence remains limited. DOI: 10.3390/medicina62050986 PMCID: PMC13208855 PMID: 42195239 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Retatrutide

Retraction Note: Cerebrolysin Attenuates Exacerbation of Neuropathic Pain, Blood-Spinal Cord Barrier Breakdown and Cord Pathology Following Chronic Intoxication of Engineered Ag, Cu or Al (50-60 nm) N

1. Neurochem Res. 2026 May 16;51(3):155. doi: 10.1007/s11064-026-04785-9. Retraction Note: Cerebrolysin Attenuates Exacerbation of Neuropathic Pain, Blood-Spinal Cord Barrier Breakdown and Cord Pathology Following Chronic Intoxication of Engineered Ag, Cu or Al (50-60 nm) Nanoparticles. Sharma HS(1), Feng L(2), Chen L(3), Huang H(4), Tian ZR(5), Nozari A(6), Muresanu DF(7)(8), Lafuente JV(9), Castellani RJ(10), Wiklund L(11), Sharma A(12). Author information: (1)International Experimental Central Nervous System Injury & Repair (IECNSIR), Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Frödingsgatan 12, LGH 1103, 75185, Uppsala, Sweden. Sharma@surgsci.uu.se. (2)Department of Neurology, Bethune International Peace Hospital, Zhongshan Road (West), Shijiazhuang, Hebei, China. (3)Department of Neurosurgery, Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing, 100700, China. (4)Beijing Hongtianji Neuroscience Academy, Beijing, 100143, China. (5)Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, USA. (6)Anesthesiology & Intensive Care, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. (7)Dept. Clinical Neurosciences, University of Medicine & Pharmacy, Cluj-Napoca- Napoca, Romania. (8)"RoNeuro" Institute for Neurological Research and Diagnostic, 37 Mircea Eliade Street, 400364, Cluj-Napoca-Napoca, Romania. (9)LaNCE, Dept. Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain. (10)Department of Pathology, University of Maryland, Baltimore, MD, 21201, USA. (11)International Experimental Central Nervous System Injury & Repair (IECNSIR), Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, 75185, Uppsala, Sweden. (12)International Experimental Central Nervous System Injury & Repair (IECNSIR), Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Frödingsgatan 12, LGH 1103, 75185, Uppsala, Sweden. aruna.sharma@surgsci.uu.se. Retraction of Neurochem Res. 2023 Jun;48(6):1864-1888. doi: 10.1007/s11064-023-03861-8. DOI: 10.1007/s11064-026-04785-9 PMCID: PMC13179879 PMID: 42143192

Mentions Cerebrolysin

Orforglipron Calcium.

1. Am J Health Syst Pharm. 2026 May 15:zxag144. doi: 10.1093/ajhp/zxag144. Online ahead of print. Orforglipron Calcium. [No authors listed] DOI: 10.1093/ajhp/zxag144 PMID: 42138709

Mentions Orforglipron

CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment.

1. Am J Cardiol. 2026 May 15;267:28-37. doi: 10.1016/j.amjcard.2026.02.030. Epub 2026 Feb 26. CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment. Gadelmawla AF(1), Hammad N(2), Atta K(3), Diaa A(4), Abouzkaly F(5), Soni K(6), Kelkar R(7), Agrawal SP(8), Ahmed R(9), Jain H(10), Passey S(11), Aronow WS(12). Author information: (1)Faculty of Medicine, Menoufia University, Menoufia, Egypt. (2)Faculty of Medicine, Port-Said University, Port-Said, Egypt. (3)Institute of Medicine, National Research Mordovia State University, Saransk, Russia. (4)Faculty of Medicine, Al-Azhar University, Cairo, Egypt. (5)Faculty of Medicine, Sohag University, Sohag, Egypt. (6)Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, New York. (7)Department of Internal Medicine, Mass General Brigham Wentworth Douglass, Dover, New Hampshire. (8)Department of Internal Medicine, New York Medical College/Landmark Medical Center, Woonsocket, Rhode Island. (9)Department of Cardiology, National Heart and Lung Institute, Imperial College London, London, UK; Department of Cardiology, Royal Brompton Hospital, London, UK; Department of Cardiology, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. (10)Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India. (11)Department of Internal Medicine, University of Connecticut Health Center, Farmington, Connecticut. (12)Departments of Medicine and Cardiology, New York Medical College and Westchester Medical Center, Macy Pavilion, Room 141, Valhalla, NY 10595, United States. Electronic address: wsaronow@aol.com. The obesity epidemic is a major health burden that enhances susceptibility to a broad spectrum of metabolic-associated comorbidities, ranging from fatty liver disease and endocrine dysfunction to traditional risks like type 2 diabetes mellitus and cardiovascular disease. Glucagon-like peptide-1 receptor agonists, including semaglutide, facilitate weight loss alongside glucose metabolism. The dual therapy CagriSema, which combines semaglutide with cagrilintide was developed. We systematically searched MEDLINE (via PubMed), Web of Science, Scopus, and Cochrane Library, from inception to July 2025, for randomized controlled trials (RCTs) comparing CagriSema with semaglutide monotherapy or placebo in patients with obesity. Four RCTs (n = 4,419) were included (CagriSema: 3,055; control: 1,364). Pooled analysis showed that CagriSema significantly reduced percent weight loss (Cohen's d: -1.38; 95% CI: -1.84 to -0.91; I² = 94.8%). CagriSema also resulted in greater absolute weight loss (MD: -11 kg), waist circumference (MD: -9.41 cm), and systolic blood pressure (MD: -7.06 mmHg). Gastrointestinal adverse events were more frequent (RR: 1.32). CagriSema therapy was associated with superior weight reduction compared with semaglutide or placebo. In conclusion, CagriSema achieves greater weight loss than semaglutide or placebo but increases gastrointestinal adverse events, warranting careful tolerability monitoring and longer-term data. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.amjcard.2026.02.030 PMID: 41759565 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions CagriSema

Effect of incretin-based therapies on blood pressure: a systematic review and meta-analysis.

1. Eur J Prev Cardiol. 2026 May 15;33(7):1210-1217. doi: 10.1093/eurjpc/zwaf560. Effect of incretin-based therapies on blood pressure: a systematic review and meta-analysis. Basile C(1)(2), Merolla A(3), Mancusi C(4), De Luca C(4), Fucile I(4), Canonico ME(5)(6), Giugliano G(4), Orso F(1), Morisco C(4), Esposito G(4). Author information: (1)ANMCO Research Center, Heart Care Foundation, Florence, Italy. (2)Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden. (3)Division of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy. (4)Department of Advanced Biomedical Science, University of Naples 'Federico II', Via Sergio Pansini 5, Naples 80131, Italy. (5)Department of Medicine, CPC Clinical Research, Aurora, USA. (6)Department of Medicine, University of Colorado, Aurora, USA. AIMS: Hypertension and obesity frequently coexist and synergistically increase cardiovascular (CV) risk. Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1-RAs), gastric inhibitory polypeptide (GIP)/GLP1-RAs, and glucagon/GIP/GLP-1RAs lead to substantial weight loss. However, their antihypertensive efficacy and safety profile have not been comprehensively quantified. Our study aimed to evaluate the effects of incretin-based therapies on office systolic blood pressure (BP) (SBP), diastolic BP (DBP), all-cause mortality, and key safety outcomes, i.e. hypoglycaemia and pancreatitis episodes, in adults with overweight or obesity. METHODS AND RESULTS: We searched PubMed, EMBASE, and ClinicalTrial.gov from inception to 30 April 2024 for randomized controlled trials (RCTs) comparing incretin-based therapy with placebo and ≥1 month of follow-up. The primary outcome was change in SBP; secondary outcomes were change in DBP, all-cause mortality, hypoglycaemia, and pancreatitis. Random effects meta-analyses generated mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs). Heterogeneity was explored with I2 statistics, subgroup analyses, and meta-regression. Eighty-five RCTs encompassing 90 977 participants (median follow-up time 8 months) met the eligibility criteria. GLP1-RAs reduced SBP by 3.4 mmHg (95% CI 2.8-4.0) and DBP by 0.9 mmHg (95% CI 0.5-1.2). A higher weight loss was significantly associated with a greater reduction in BP. The most significant BP reduction was associated with dual (SBP 5.1 mmHg; DBP 1.8 mmHg) and triple (SBP 6.6 mmHg; DBP 2.1 mmHg) receptor agonists. All-cause mortality was reduced by 18% (RR 0.82, 95% CI 0.76-0.90). Incretin-based therapy did not increase the risk of hypoglycaemia (RR 1.05, 95% CI 0.83-1.33) or pancreatitis (RR 0.84, 95% CI 0.61-1.15). CONCLUSION: Incretin-based therapy led to a modest but clinically meaningful BP reduction and lower all-cause mortality in adults with overweight or obesity, without excess in hypoglycaemia or pancreatitis episodes. There was a significant association between weight loss and the reduction in SBP and DBP. Dual and triple agonists exhibited the most pronounced antihypertensive effect. These findings support the use of incretin-based therapies as part of an integrated and multidisciplinary approach to managing obesity and hypertension, with multiple agonists showing particular promise. Our findings also underscore the need for long-term RCTs to clarify weight-independent mechanisms and the durability effect of BP reduction. Plain Language Summary: Incretin-based therapy, now widely used for weight loss, also modestly reduces blood pressure and mortality, providing an additional health benefit to people with obesity or diabetes.Across 85 clinical trials (more than 90 000 adults), incretin-based therapy lowered systolic blood pressure by about 3 mmHg; the most significant falls occurred with the dual and triple agonists, and every kilogram lost made the reduction larger.Incretin-based therapy use was associate

Mentions Retatrutide

Differing Presentations of Excess Visceral Abdominal Fat in People Living With HIV: Two Clinical Cases Highlighting Distinct Therapeutic Pathways With Tesamorelin and Glucagon-Like Peptide-1 Receptor

1. Clin Infect Dis. 2026 May 15;82(Supplement_4):S87-S91. doi: 10.1093/cid/ciag121. Differing Presentations of Excess Visceral Abdominal Fat in People Living With HIV: Two Clinical Cases Highlighting Distinct Therapeutic Pathways With Tesamorelin and Glucagon-Like Peptide-1 Receptor Agonists. Beach R(1), Tims-Cook Z(2), McGary CS(3), Thote T(3). Author information: (1)Division of General Internal Medicine McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA. (2)Faebris, Atlanta, Georgia, USA. (3)Theratechnologies Inc, Medical Affairs, Montreal, Quebec, Canada. BACKGROUND: Excess visceral abdominal fat (EVAF) is a prevalent metabolic complication among people living with HIV-1 (PLWH), occurring even in individuals with normal or mildly elevated body mass index (BMI). This pattern of fat accumulation is associated with metabolic dysfunction, cardiovascular risk, and reduced quality of life. Since EVAF can present without generalized obesity, weight-based assessments may fail to identify it; moreover, addressing EVAF warrants distinct approaches based on a patient's presentation. Two therapeutic classes have been studied in this setting: growth hormone-releasing hormone analog (tesamorelin), which selectively reduces visceral fat, and glucagon-like peptide (GLP-1) receptor agonists, which induces generalized weight loss in a nonspecific way. CASE PRESENTATIONS: Two adults with well-controlled HIV presented with central adiposity. The first patient demonstrated a nonobese visceral adiposity phenotype characterized by increased waist circumference (WC) and a BMI of 27 kg/m². Treatment with tesamorelin led to marked reductions in WC, improved lipid levels, and enhanced functional well-being. The second patient, a woman with higher BMI representative of obesity, received a GLP-1; however, her intermittent access to the medication resulted in fluctuating weight trends and persistent abdominal fat. Incorporation of tesamorelin provided a more targeted approach to reduce visceral adiposity in this context. RESULTS: Both cases demonstrated that EVAF may persist independent of BMI category and may respond differently to therapies targeting generalized obesity versus selective visceral abdominal fat. CONCLUSIONS: These cases highlight the heterogeneity of EVAF in PLWH and support individualized management strategies informed by fat distribution rather than weight alone. © The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. DOI: 10.1093/cid/ciag121 PMID: 42139091 [Indexed for MEDLINE] Conflict of interest statement: Potential conflicts of interest. R. B.: Speaker honoraria: Theratechnologies, Gilead, and ViiV. Z. T. C.: Speaker honoraria: Theratechnologies and ViiV. C. C. and T. T.: Employee of Theratechnologies. The content reflects clinical observations and is intended for educational purposes consistent with scientific publication standards.

Mentions Tesamorelin

Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.

1. Nat Med. 2026 May 13. doi: 10.1038/s41591-026-04386-7. Online ahead of print. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Aronne LJ(1), Horn DB(2), le Roux CW(3)(4), Chao AM(5), Ho W(6), Halpern B(7), Griffin R(8), Xie C(8), Valderas EG(8), Lee CJ(8), Ribeiro A(8), Hyman DM(8), Glass L(8), Xavier N(8). Author information: (1)Comprehensive Weight Control Center, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, New York, NY, USA. ljaronne@med.cornell.edu. (2)Center for Obesity Medicine and Metabolic Performance, Departments of Surgery and Internal Medicine, University of Texas McGovern Medical School, Houston, TX, USA. (3)Metabolic Medicine, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland. (4)Diabetes Research Centre, Ulster University, Coleraine, UK. (5)Johns Hopkins School of Nursing, Baltimore, MD, USA. (6)Keck School of Medicine of University of Southern California, Los Angeles, CA, USA. (7)Obesity Center, Nove de Julho Hospital, São Paulo, Brazil. (8)Eli Lilly and Company, Indianapolis, IN, USA. Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging. Orforglipron, a once-daily oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated weight loss efficacy, improvements in cardiometabolic risk factors, and safety generally similar to injectable GLP-1 receptor agonists. Here this double-blind, placebo-controlled trial randomized participants previously treated with tirzepatide (cohort 1: N = 205) or semaglutide (cohort 2: N = 171) during the SURMOUNT-5 study to orforglipron once daily or placebo. Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% (s.e.m. 4.05) of body weight reduction with orforglipron compared with an MBE of 49.2% (s.e.m. 3.92) with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval 14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52. Cohort 2 participants who achieved body weight plateau maintained an MBE of 79.3% (s.e.m. 4.42) of body weight reduction with orforglipron compared with an MBE of 37.6% (s.e.m. 7.46) with placebo, resulting in an estimated treatment difference of MBE 41.7 (95% confidence interval 24.4 to 59.0); P < 0.001; treatment-regimen estimand) at week 52. All key secondary endpoints were met. The most common adverse events were gastrointestinal effects, which were mostly mild to moderate in severity. These data demonstrate orforglipron's potential as a globally scalable option for minimizing weight changes after injectable therapy. Trial limitations include the absence of a comparator arm involving continued use of injectable obesity-management medications and the trial's 1-year duration. ClinicalTrials.gov registration: NCT06584916 . © 2026. The Author(s). DOI: 10.1038/s41591-026-04386-7 PMID: 42120723 Conflict of interest statement: Competing interests: L.J.A. reports receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences and Versanis and being a shareholder of ERX Pharmaceuticals, Gelesis, Intellihealth and Jamieson Wellness. D.B.H. reports consulting for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Zealand and has received institutional research funding from Eli Lilly and Company, KVK Tech, Novo Nordisk and Weight Watchers. C.W.l.R. has acted as a consultant for Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Currax Pharmaceuticals LLC, Eli Lilly and Company, F. Hoffmann-La Roche AG, Johnson and Johnson, Medtronic and Novo Nordisk. A.M.C. has served on advisory

Mentions Orforglipron

Multi-Layer Magnetic Shields Based on Fe-Based Nanocrystalline and Co-Based Amorphous Ribbons.

1. Materials (Basel). 2026 May 11;19(10):1986. doi: 10.3390/ma19101986. Multi-Layer Magnetic Shields Based on Fe-Based Nanocrystalline and Co-Based Amorphous Ribbons. Liang Y(1)(2), Liu B(1)(2), Ma H(2), Pan L(2), He A(2)(3), Dong Y(2)(3), Man Q(2)(3), Li J(2)(3). Author information: (1)School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China. (2)Zhejiang Key Laboratory of Magnetic Materials and Applications, Ningbo Institute of Materials Technology & Engineering, Ningbo 315201, China. (3)University of Chinese Academy of Sciences, Beijing 100049, China. We constructed a multi-layer composite magnetic shield composed of Fe-based nanocrystalline (FN) and Co-based amorphous (CA) ribbons, and focused on the influence of the number of layers and their arrangement on the shielding effectiveness (SE). Finite element analysis (FEA) and layer-by-layer inversion calculations were performed to analyze the attenuation process of the magnetic field between shield layers. Increasing the number of shield layers improves the maximum value of SE (SEmax) and significantly broadens the working range (WWR). In a weak magnetic field, CA exhibits higher shielding performance, whereas FN is better in a strong magnetic field. The FN/FN/CA combination (FN is closer to the field source) exhibits an SEmax of up to 51.7 dB within a WWR of 674.3 A/m, and demonstrates a 14.4% improvement in SE compared to FN/FN/FN combination across the entire tested magnetic field range. Finally, a gradient layering design is proposed that enables each layer to operate within its optimal permeability range, thereby improving the overall SE and broadening the effective working magnetic field range. DOI: 10.3390/ma19101986 PMCID: PMC13208922 PMID: 42195624 Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Semax

Glycyl-L-histidyl-L-lysine-Cu2(+) (GHK-Cu) Attenuates CuSO(4) or LPS induced-inflammation in Zebrafish larvae model.

1. Eur J Pharmacol. 2026 May 10;1023:178880. doi: 10.1016/j.ejphar.2026.178880. Epub 2026 Apr 15. Glycyl-L-histidyl-L-lysine-Cu2(+) (GHK-Cu) Attenuates CuSO(4) or LPS induced-inflammation in Zebrafish larvae model. Hu J(1), Zhang C(1), Wang F(2). Author information: (1)Yunnan Botanee Bio-Technology Group Co., Ltd, Kunming, Yunnan, 650106, China; Yunnan Characteristic Plant Extraction Laboratory, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan, 650106, China; Shanghai Jiyan Bio-pharmaceutical Co., Ltd., Shanghai, 200000, China. (2)Yunnan Botanee Bio-Technology Group Co., Ltd, Kunming, Yunnan, 650106, China; Yunnan Characteristic Plant Extraction Laboratory, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan, 650106, China; Shanghai Jiyan Bio-pharmaceutical Co., Ltd., Shanghai, 200000, China. Electronic address: wangfeifeiBTN@126.com. Inflammation serves as a basic defense mechanism against both internal and external threats, while the unresolved or excessive inflammation can lead to irreversible tissue damage. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu), a bioactive tripeptide complex known for its anti-aging and tissue repair properties, is extensively utilized in dermatological and hair care formulations. However, the role of GHK-Cu in regulating inflammation is less known. In this study, we explored the anti-inflammatory effects of GHK-Cu against the acute inflammation induced by copper sulfate (CuSO4) and lipopolysaccharide (LPS) in zebrafish larvae. GHK-Cu notably decreased the migration of neutrophils and macrophages, suppressed the expression of pro-inflammatory cytokines (tnf-a, il-1β, il6) and increased the expression of the anti-inflammatory cytokine il-10. Moreover, GHK-Cu mitigated oxidative stress by reducing levels of nitric oxide (NO) and reactive oxygen species (ROS), and improved superoxide dismutase (SOD) activity. Furthermore, pathway analysis revealed that GHK-Cu administration downregulated the JAK1 pathway. In summary, this study highlights the dual role of GHK-Cu in both anti-inflammatory and anti-oxidant properties, which provides the theoretical evidences supporting its addition as a functional cosmetic ingredient. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.ejphar.2026.178880 PMID: 41997403 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions GHK-Cu

CVOT Summit Report 2025: advances along the cardiovascular-kidney-metabolic disease continuum.

1. Cardiovasc Diabetol. 2026 May 6;25(1):142. doi: 10.1186/s12933-026-03140-0. CVOT Summit Report 2025: advances along the cardiovascular-kidney-metabolic disease continuum. Schnell O(1), Agarwal A(2)(3)(4), Azizi M(5)(6), Ballwieser D(7), Barnard-Kelly K(8), Battelino T(9)(10), Ballwieser D(7), Blüher M(11)(12), Bugianesi E(13), Cebrian A(14)(15), Ceriello A(16), Choudhary P(17), Danne T(18), Dayan CM(19), Del Prato S(20), Eckel RH(21), Fioretto P(22), Garvey T(23), Green JB(24), Heerspink HJL(25), Holman RR(26), Itzhak B(27)(28), Jacob S(29), Jhund PS(30), Ji L(31), Judge PK(32)(33), Khunti K(17), Korenjak M(34)(35), Krentz AJ(36), Lambrinou E(37), Libby P(38), Mader JK(39), Mann JFE(40)(41), Marx N(42), Mathieu C(43), McMurray JJV(44), Müller-Wieland D(42), Papanas N(45), Patel DC(46), Pfeiffer AFH(47)(48), Reger-Tan S(49), Rodbard HW(50), Rosano GMC(51)(52), Saboo B(53), Sato N(54), Solomon SD(55), Standl E(56), Tacke F(57), Topsever P(58), Wanner C(59)(60), Wharton S(61)(62), Young V(62). Author information: (1)Forschergruppe Diabetes E. V., Helmholtz Center Munich, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany. oliver.schnell@lrz.uni-muenchen.de. (2)Division of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, AB, Canada. (3)Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. (4)MAGIC Evidence Ecosystem Foundation, Oslo, Norway. (5)Université Paris Cité, INSERM Centre d'Investigation Clinique 1418, Paris, France. (6)Department of Hypertension, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. (7)Wort & Bild Verlag, Baierbrunn, Germany. (8)Southern Health NHS Foundation Trust, Southampton, UK. (9)University Medical Center, Ljubljana, Slovenia. (10)Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. (11)Helmholtz Institute for Metabolic, Obesity, and Vascular Research (HI-MAG), Leipzig, Germany. (12)Faculty of Medicine, University of Leipzig, Leipzig, Germany. (13)Department of Medical Sciences, University of Turin, Turin, Italy. (14)Cartagena Casco Health Center, 30201, Murcia, Spain. (15)Murcian Institute for Biosanitary Research (IMIB), Murcia, Spain. (16)IRCCS MultiMedica, Milan, Italy. (17)Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK. (18)NOVA Medical School, Lisbon, Portugal. (19)Cardiff University School of Medicine, Cardiff, UK. (20)Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. (21)University of Colorado Anschutz Medical Campus, Aurora, CO, USA. (22)Faculty of Medicine, University of Padova, Padua, Italy. (23)Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. (24)Duke Clinical Research Institute, Duke University, Durham, NC, USA. (25)Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. (26)Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. (27)Clalit Health Services, Haifa, Israel. (28)Technion Faculty of Medicine, Haifa, Israel. (29)Department of Internal Medicine, Endocrinology, and Diabetology, Cardiometabolic Institute, Villingen-Schwenningen, Germany. (30)Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, British Heart Foundation, University of Glasgow, Glasgow, UK. (31)Peking University People's Hospital, Xicheng District, Beijing, China. (32)Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. (33)Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LF, UK. (34)European Liver Patients' Association, Brussels, Belgium. (35)Faculty of Government and European Studies, New University, Kranj, Slovenia. (36)School

Mentions Orforglipron

The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways.

1. Biogerontology. 2026 May 5;27(3):100. doi: 10.1007/s10522-026-10444-x. The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways. Wen H(#)(1), Zhao K(#)(2), Luo X(1), Pu J(1)(3), Li Y(1), Dou Y(1), He J(1), Nie X(1), Ke Y(1), Zhou W(4). Author information: (1)School of Medicine, Yunnan University, Kunming, 650091, China. (2)School of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, China. (3)The Affiliated Hospital of Yunnan University, Kunming, 650021, China. (4)School of Medicine, Yunnan University, Kunming, 650091, China. whzhou@ynu.edu.cn. (#)Contributed equally Aging is a complex biological process characterized by progressive functional decline across tissues and increased susceptibility to age-related diseases, with oxidative stress being a key contributing factor. Glycine-Histidine-Lysine (GHK), a naturally occurring tripeptide present in human plasma and urine, possesses potent antioxidant properties; however, its broader anti-aging potential remains inadequately explored. In this study, we employed the model organism Caenorhabditis elegans to systematically investigate the anti-aging effects of GHK-Cu (GHK complexed with copper) and elucidate its underlying molecular mechanisms. Our results demonstrated that GHK-Cu significantly extended lifespan of C. elegans and ameliorated mutiple aging-related phenotypes, including enhanced resistance to oxidative and thermal stress, improved motility, pharyngeal pumping, defecation rhythm, and reduced lipofuscin/lipid accumulation. Mechanistically, GHK-Cu preserved mitochondrial function by increasing mitochondrial membrane potential, alleviating age-related mitochondrial network fragmentation, shifting mitochondrial dynamics toward fusion via regulating drp-1 and fzo-1 expression, and promoting ATP biosynthesis. Meanwhile, GHK-Cu activating DAF-16 and SKN-1 pathway, and upregulating sod-3, gst-4, gcs-1, lys-7 and lys-8. This study provides the first mechanistic evidence that GHK-Cu delays aging through coordinated regulation of mitochondrial function and activation of both DAF-16 and SKN-1 pathways. Our findings identify novel molecular targets for developing anti-aging interventions and underscore the potential of GHK-Cu's as a multifaceted geroprotective compound. © 2026. The Author(s), under exclusive licence to Springer Nature B.V. DOI: 10.1007/s10522-026-10444-x PMID: 42084774 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: The authors declare no competing interests.

Mentions GHK-Cu

Tirzepatide-associated interstitial kidney injury.

1. JCEM Case Rep. 2026 May 5;4(6):luag125. doi: 10.1210/jcemcr/luag125. eCollection 2026 Jun. Tirzepatide-associated interstitial kidney injury. Eldib M(1), Mendpara V(2), Herlitz L(3), Rodriguez Alvarez P(1), Dhingra J(4), Khan LZ(1). Author information: (1)Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH 44195, USA. (2)Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. (3)Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195, USA. (4)Department of Kidney Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. We report a case of interstitial nephritis, likely secondary to tirzepatide. A 66-year-old man with type 2 diabetes, stage 3b chronic kidney disease, and other metabolic comorbidities experienced a progressive decline in renal function. Serum creatinine rose from 1.1 mg/dL (SI: 97.2 µmol/L) to 2.11 mg/dL (SI: 186.5 µmol/L) (reference range, 0.6-1.2 mg/dL [SI: 53-106 µmol/L]); estimated glomerular filtration rate (eGFR) fell from 68 to 34 mL/min/1.73 m2 over 8 months while receiving escalating doses of tirzepatide. Despite cessation of other medications and supportive care, renal dysfunction persisted. Kidney biopsy revealed chronic active tubulointerstitial nephritis with eosinophilic infiltrates and fibrosis implicating tirzepatide as the likely cause. Discontinuation of tirzepatide and initiation of prednisone resulted in significant improvement (serum creatinine measured 1.68 mg/dL (SI: 148.5 µmol/L) at 1 month and stabilized at 1.78 mg/dL (SI: 157.3 µmol/L); eGFR improved from 34 mL/min/1.73 m2 to 42 mL/min/1.73 m2 by 3 months). This case highlights a rare, biopsy-proven adverse renal effect of tirzepatide and underscores the importance of considering interstitial nephritis in patients with unexplained kidney injury on incretin mimetic therapy. Although glucagon-like peptide-1 receptor agonists benefits outweigh rare risks of nephrotoxicity, regular monitoring of creatinine monitoring is advised. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. DOI: 10.1210/jcemcr/luag125 PMCID: PMC13142148 PMID: 42093865

Mentions Tirzepatide

Endothelium-Dependent Nitric Oxide-Mediated Vasorelaxant Effects of BPC 157 in Human Internal Mammary Artery.

1. J Clin Med. 2026 May 2;15(9):3488. doi: 10.3390/jcm15093488. Endothelium-Dependent Nitric Oxide-Mediated Vasorelaxant Effects of BPC 157 in Human Internal Mammary Artery. Yildirim AK(1), Dastan AO(2), Demeli Ertus M(3), Ensarioglu M(4), Karabacak K(5), Pehlivanoglu B(2). Author information: (1)Department of Cardiovascular Surgery, Gulhane Training and Research Hospital, Ankara 06010, Turkey. (2)Department of Physiology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey. (3)Department of Physiology, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak 67600, Turkey. (4)Department of Anesthesiology and Reanimation, Gulhane Training and Research Hospital, Ankara 06010, Turkey. (5)Department of Cardiovascular Surgery, Gulhane Training and Research Hospital, University of Health Sciences, Ankara 06010, Turkey. Background/Objectives: Body Protection Compound-157 (BPC 157) is a stable gastric pentadecapeptide with cytoprotective, pro-angiogenic, and nitric oxide (NO)-modulating properties that has gained increasing attention for its therapeutic potential. Although vasodilatory effects have been demonstrated in animal models, functional evidence in human arterial tissue remains limited. This study investigated the effects of BPC 157 on vascular tone in human internal mammary artery (IMA) rings and evaluated the contribution of endothelial NO signaling. Methods: Residual IMA segments obtained from elective coronary artery bypass graft surgeries (n = 12) were dissected into endothelium-intact and endothelium-denuded rings. Following equilibration, the rings were challenged by phenylephrine (PheE; 3 × 10-6 M) to induce contraction. Cumulative concentration-response curves of BPC 157 (0.01-1 mg/mL) for five consecutive doses were constructed. The involvement of NO was assessed by BPC 157 dose-response curves in the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10-6 M) pre-incubated rings. Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed. Results: BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both groups, with significantly greater relaxation in endothelium-intact rings (p < 0.05). L-NAME increased contractile responsiveness in intact rings and attenuated BPC 157-induced relaxation. Under NOS inhibition, differences between groups progressively diminished and concentration-response curves converged at higher concentrations. Emax analysis demonstrated that endothelial integrity markedly enhanced maximal vasorelaxation, whereas this advantage was largely abolished after NOS inhibition. Conclusions: BPC 157 induces concentration-dependent vasorelaxation in human arterial tissue, predominantly mediated via an endothelium-dependent NO pathway. Endothelial integrity primarily enhances maximal efficacy, while residual effects indicate additional mechanisms. These findings provide early mechanistic evidence for the vascular activity of BPC 157, although further molecular and in vivo studies are required to clarify its clinical relevance. DOI: 10.3390/jcm15093488 PMCID: PMC13163310 PMID: 42123221 Conflict of interest statement: The authors declare no conflicts of interest.

Mentions BPC-157

Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.

1. Endocrinol Diabetes Metab. 2026 May;9(3):e70247. doi: 10.1002/edm2.70247. Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis. Kamrul-Hasan ABM(1), Khalil I(2), Mahajan K(3), Dutta D(4), Banerjee M(5)(6), Pappachan JM(7)(8)(9). Author information: (1)Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. (2)Department of Medicine, Dhaka Medical College and Hospital, Dhaka, Bangladesh. (3)Department of Cardiology, Himachal Heart Institute, Mandi, Himachal Pradesh, India. (4)Department of Endocrinology, CEDAR Superspeciality Healthcare, New Delhi, India. (5)Department of Endocrinology, Rabindranath Tagore International Institute of Cardiac Sciences, RN Tagore Hospital, Kolkata, West Bengal, India. (6)Department of Endocrinology, Ramakrishna Mission Seva Pratishthan (RKMSP) & Vivekananda Institute of Medical Sciences (VIMS), Kolkata, West Bengal, India. (7)Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston, UK. (8)Faculty of Science, Manchester Metropolitan University, Manchester, Greater Manchester, UK. (9)Department of Endocrinology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India. BACKGROUND: Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework. METHODS: We conducted a frequentist random-effects NMA of randomized controlled trials comparing novel ABTs with placebo or active comparators in R. Primary outcome was the percent change in body weight from baseline. Secondary outcomes included absolute weight changes, anthropometric measures, and overall and specific GI adverse events (AEs). Treatments (including dose strata) were compared with placebo within a single network and ranked using P scores. RESULTS: Six trials (N = 4642; 12-68 weeks) were included. Compared with placebo, high dose (HiD) subcutaneous amycretin produced the largest reduction in percent body weight (mean difference -23.95%; P score 1.00), followed by HiD eloralintide (-18.01%; P score 0.89) and HiD CagriSema (-17.18%; P score 0.85), all exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). Almost similar patterns were observed for absolute weight, body mass index, waist circumference and categorical weight-loss thresholds. GI AEs, nausea, vomiting and constipation were more common with HiD ABTs, especially oral amycretin and CagriSema, while diarrhoea mainly increased with semaglutide 2.4 mg. Only HiD CagriSema increased AE-related discontinuation. CONCLUSIONS: Novel ABTs, such as HiD amycretin, CagriSema and eloralintide, may induce substantial short- to medium-term weight loss but may also increase GI AEs; given sparse, low-certainty data, these findings are preliminary and require confirmation in larger trials. TRIAL REGISTRATION: The meta-analysis was registered in PROSPERO (CRD420261340457). The review protocol summary can be accessed at the PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/view/CRD420261340457). © 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. DOI: 10.1002/edm2.70247 PMID: 42175595 [Indexed for MEDLINE]

Mentions CagriSema

Use of nootropics in Alzheimer's disease: An analysis of regulatory positions and drug policies in the countries of the Commonwealth of Independent States.

1. Int J Risk Saf Med. 2026 May;37(2):257-264. doi: 10.1177/09246479251410817. Epub 2025 Dec 30. Use of nootropics in Alzheimer's disease: An analysis of regulatory positions and drug policies in the countries of the Commonwealth of Independent States. Alexandrova EG(1), Abakumova TR(1), Ziganshina LE(2)(3). Author information: (1)Department of Biochemistry, Biotechnology and Pharmacology, Kazan (Volga Region) Federal University, Kazan, Russia. (2)Department of General and Clinical Pharmacology, Peoples' Friendship University of Russia Named After Patrice Lumumba, RUDN University, Moscow, Russia. (3)Kazan State Medical University, Kazan, Russia. ObjectiveTo analyse regulatory positions and drug policies of the Commonwealth of Independent States (CIS), compared to those of the EU, UK, USA i of the nootropics, used in Russia for Alzheimer's disease.MethodsWe searched E-library to reveal the list of nootropics used and studied in Russia for Alzheimer's disease. We assessed official pharmaceutical registries of nine countries for registration status of identified nootropics, 7 National Essential Medicines Lists (EML), and four clinical practice guidelines (CPG) on Alzheimer's disease. We compared the results of Russia with other countries regulatory and policy positions.ResultsE-Library searches identified 11 nootropicspiracetam, citicoline, idebenone, vinpocetine, choline alfoscerate, Cerebrolysin®, Kortexin®, ethylmethylhydroxypyridine succinate, glycine, nicergoline, nimodipine. Eight nootropic have registration for use in all CIS countries (excluding idebenone, nimodipine), four (piracetam, nimodipine, nicergoline, idebenone) - in UK, nimodipine - in the USA, and idebenone - in EU. National EMLs included: nine nootropics (Russia), 8 - Belarus and Kazakhstan, 4 - Uzbekistan, 2 - Armenia. The studied nootropic agents are not included on the WHO Model EML and on the National EML of the Kyrgyz Republic. They are not listed in the CPG for Treatment of dementia and Alzheimer's disease in the USA, the EU, and the UK. Russian CPGs for Alzheimer's disease recommend Cerebrolysin® and choline alfoscerate.ConclusionsThe studied nootropics are registered for use and listed on National EMLs of Russia, Armenia, Belarus, Kazakhstan, Uzbekistan. None is included on the WHO Model EML and the National EML of Kyrgyzstan, Only CPG of the RF recommend using two nootropics as adjuvant therapy of Alzheimer's disease, Cerebrolysin® and choline alfoscerate. CPG of the European Union, the United Kingdom, and the USA do not mention nootropics as potential treatment options for Alzheimer's disease. DOI: 10.1177/09246479251410817 PMID: 41467376 [Indexed for MEDLINE] Conflict of interest statement: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mentions Cerebrolysin

Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives.

1. Int J Mol Sci. 2026 Apr 27;27(9):3890. doi: 10.3390/ijms27093890. Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives. Renke G(1), Chinellato L(2). Author information: (1)Nutrindo Ideais Performance and Nutrition Research Center, Rio de Janeiro 22411-040, Brazil. (2)Instituto Lucas Chinellato, Campinas 13092-133, Brazil. Therapeutic peptides are short chains of amino acids used to treat metabolic and endocrine conditions such as obesity and type 2 diabetes. While several peptide drugs have undergone rigorous approval processes that evaluate both safety and efficacy, novel, unapproved compounds have emerged and are rapidly expanding into preventive medicine and performance enhancement. Our objective is to present the effects, clinical applications, safety profiles, and regulatory status of prominent peptides used to treat several conditions. We reviewed 106 articles, prioritizing systematic reviews, meta-analyses, and randomized controlled trials in the PubMed, ScienceDirect, and SciELO databases. Our results suggest that therapeutic peptides are a promising tool for treating type 2 diabetes and obesity, for skin rejuvenation, and as hormone analogs for specific diseases and conditions. Although these are strategic and innovative options that can improve health, performance, and longevity, further studies are needed before most new peptides can be used safely in humans. DOI: 10.3390/ijms27093890 PMCID: PMC13164565 PMID: 42123471 [Indexed for MEDLINE] Conflict of interest statement: G.R. receives grants for clinical research and development from Cellgenic. L.C. declares no conflicts of interest.

Mentions GHK-Cu

Retraction: Regional Comparison of the Neurogenic Effects of CNTF-Derived Peptides and Cerebrolysin in AβPP Transgenic Mice.

1. J Alzheimers Dis. 2026 Apr 21:13872877261442048. doi: 10.1177/13872877261442048. Online ahead of print. Retraction: Regional Comparison of the Neurogenic Effects of CNTF-Derived Peptides and Cerebrolysin in AβPP Transgenic Mice. [No authors listed] Retraction of J Alzheimers Dis. 2011;27(4):743-52. doi: 10.3233/JAD-2011-110914. DOI: 10.1177/13872877261442048 PMID: 42015030

Mentions Cerebrolysin

Microenvironment-responsive injectable dynamic hydrogel for sequential antioxidant and tissue regeneration therapy of radiation-induced skin injury.

1. Bioact Mater. 2026 Apr 21;63:778-794. doi: 10.1016/j.bioactmat.2026.03.057. eCollection 2026 Sep. Microenvironment-responsive injectable dynamic hydrogel for sequential antioxidant and tissue regeneration therapy of radiation-induced skin injury. Yu X(1), Yang T(1), Bei Z(1), Liu J(1), Song Y(2), Wang Q(2), Li J(1), Liang S(3), Qian Z(1). Author information: (1)Institute of Biomaterials and Nanomedicine, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. (2)Department of Radiation Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. (3)Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Radiotherapy is essential for cancer treatment, yet radiation-induced skin injury (RISI) remains a major clinical challenge due to reactive oxygen species (ROS) accumulation, metabolic dysregulation, and the limited efficacy of single-modality therapies in modulating the oxidative-inflammatory microenvironment. To overcome this limitation, we have developed a multifunctional injectable hydrogel, HCG@CDs, by cross-linking biocompatible carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) conjugated to the Glycyl-L-Histidyl-L-Lysine-Copper(II) complex (GHK-Cu 2+ ) via dynamic Schiff-base linkages. Carbon dots (CDs) possessing superoxide dismutase (SOD)-like activity are uniformly dispersed within this three-dimensional dynamic network, creating an integrated platform for full-cycle therapy. The system exhibits intelligent, pH-responsive release behavior, whereby CDs are rapidly liberated in the acidic wound microenvironment to efficiently scavenge ROS and mitigate early-stage oxidative stress. Subsequently, GHK-Cu 2+ is released in a sustained manner to synergistically promote tissue repair by modulating inflammation, enhancing cell migration and proliferation, and facilitating collagen deposition. In vitro and in vivo evaluations have confirmed that the HCG@CDs hydrogel effectively alleviates radiation-induced oxidative damage and inflammatory responses, significantly accelerating the healing of skin wounds. Overall, this multifunctional hydrogel demonstrates great potential in accelerating the healing of RISI through multi-target synergistic regulation, highlighting its significant promise for clinical wound management and skin regeneration. © 2026 Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. DOI: 10.1016/j.bioactmat.2026.03.057 PMCID: PMC13123401 PMID: 42058630 Conflict of interest statement: Zhiyong Qian is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests.

Mentions GHK-Cu

Potassium-Competitive Acid Blocker Increases Ileal Permeability and Exacerbates Ileal Inflammation under Stress Conditions in a Mouse Model of Eosinophilic Enteritis.

1. Digestion. 2026 Apr 20:1-18. doi: 10.1159/000552062. Online ahead of print. Potassium-Competitive Acid Blocker Increases Ileal Permeability and Exacerbates Ileal Inflammation under Stress Conditions in a Mouse Model of Eosinophilic Enteritis. Yamamoto K, Tanaka F, Nishida Y, Maruyama H, Ominami M, Nadatani Y, Otani K, Fukunaga S, Hosomi S, Fujiwara Y. INTRODUCTION: Potassium-competitive acid blockers (P-CABs) have been empirically administered to treat non-esophageal eosinophilic gastrointestinal diseases, although their efficacy remains unproven. Our previous findings demonstrated that psychological stress impairs the intestinal barrier and exacerbates eosinophilic enteritis (EoN) in a mouse model. Moreover, we demonstrated that P-CAB increased intestinal permeability under psychological stress. The aim of this study is to clarify the hypothesis that P-CAB exacerbate EoN by increasing intestinal permeability under stressful conditions. METHODS: An EoN model was established in BALB/c mice using ovalbumin (OVA) sensitization and challenge. Mice were subjected to water avoidance stress (WAS) or sham stress (SS) and were administered P-CAB or saline as a vehicle. The ileum was collected for the analysis of ileal microscopic inflammation, mRNA and protein expression levels of T helper type 2 (Th2) cytokines, and ex vivo ileal permeability using a Ussing chamber. RESULTS: Compared with the WAS + Vehicle group, WAS + P-CAB significantly exacerbated the incidence of diarrhea, villus/crypt ratio, eosinophil and mast cell counts, mRNA and protein levels of Th2 cytokines, OVA-specific immunoglobulin E protein levels, and ileal permeability. Larazotide acetate, a zonulin inhibitor, significantly improved ileal inflammation and decreased ileal permeability in the WAS + P-CAB-treated EoN mice. CONCLUSIONS: P-CAB increased ileal permeability and exacerbated EoN under stressful conditions. Furthermore, a zonulin inhibitor demonstrated therapeutic effects in EoN with P-CAB under stressful conditions. S. Karger AG, Basel. DOI: 10.1159/000552062 PMID: 42008374

Mentions Larazotide

Biochemical and Pharmacological Studies on Kynurenic Acid Metabolism in the Helix pomatia-Snail Model of Learning and Memory.

1. Biomolecules. 2026 Apr 18;16(4):603. doi: 10.3390/biom16040603. Biochemical and Pharmacological Studies on Kynurenic Acid Metabolism in the Helix pomatia-Snail Model of Learning and Memory. Baran H(1)(2), Kronsteiner C(1). Author information: (1)Karl Landsteiner Research Institute for Neurochemistry, Neuropharmacology, Neurorehabilitation and Pain Treatment Mauer, Neuropsychiatric Hospital Mauer, Hausmenninger Straße 221, 3362 Mauer bei Amstetten, Austria. (2)Department of Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, Austria. Kynurenic acid (KYNA), a metabolite of the L-kynurenine pathway of L-tryptophan degradation, is an endogenous blocker of glutamate ionotropic excitatory amino acid (EAA) receptors and nicotinic acetylcholine receptors (nAChRs). KYNA plays a significant role in various neuropsychiatric disorders and the aging process. Some researchers have suggested that KYNA may contribute to memory impairment. In this study, we examined the impact of L-kynurenine (a KYNA substrate) and the anti-dementia drugs D-cycloserine and Cerebrolysin on kynurenine aminotransferase (KAT) activity, an enzyme forming KYNA, in liver homogenates of Helix pomatia snails. Furthermore, a memory model was established using these snails, wherein tentacle shortening served as an indicator of learning activity. In vitro experiments on Helix pomatia demonstrated the significant impact of L-kynurenine and anti-dementia drugs on KYNA synthesis. KYNA levels increased significantly in the presence of L-kynurenine in liver homogenate. However, KYNA formation decreased when anti-dementia drugs, including Cerebrolysin or D-cycloserine, were administered to the snails' liver homogenate. L-kynurenine has been shown to impair the learning process in vivo in snails, but an anti-dementia drug has been demonstrated to reverse this effect. Significant inhibition of tentacle lowering was observed in response to L-kynurenine treatment, which corresponded with elevated KYNA levels in the central nervous system. Administering D-cycloserine or Cerebrolysin alongside L-kynurenine reversed its effects. The Helix pomatia memory model is a valuable tool for studying learning and memory formation in various conditions and in the presence of different pharmacological agents. A drug or natural extract that blocks KYNA synthesis has the ability to increase tentacle lowering and could be considered an anti-dementia agent. Furthermore, this metabolite may also protect against aging and delay damage to the central nervous system related to memory. DOI: 10.3390/biom16040603 PMCID: PMC13115359 PMID: 42072724 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Cerebrolysin

Digitally Guided Hybrid Maxillary Expansion with Supragingival Mandibular Miniplates for Class III Correction in Late Adolescents: A Pilot Clinical Study.

1. J Clin Med. 2026 Apr 17;15(8):3070. doi: 10.3390/jcm15083070. Digitally Guided Hybrid Maxillary Expansion with Supragingival Mandibular Miniplates for Class III Correction in Late Adolescents: A Pilot Clinical Study. Arcos I(1), Walter A(1), Marc T(1), Clusellas N(1), Puigdollers A(1). Author information: (1)Facultat d'Odontologia, Departament d'Ortodoncia, Universitat Internacional de Catalunya, C/Josep Trueta s/n, 08195 Barcelona, Spain. Background: Management of skeletal Class III malocclusion of maxillary origin in late adolescence remains challenging, as conventional tooth-borne orthopedic approaches show reduced effectiveness at advanced stages of skeletal maturation. Minimally invasive, bone-anchored alternatives supported by digital workflows may improve clinical feasibility and patient acceptance. Objective: To describe a digitally guided clinical protocol combining a hybrid maxillary expander and supragingival mandibular miniplates, and to explore skeletal and dentoalveolar outcomes in late adolescents. Methods: This retrospective pilot clinical study included ten late adolescents (mean age 16.0 ± 1.3 years; range 13.8-17.7) in advanced skeletal maturation stages (CS4-CS6) with skeletal Class III malocclusion of maxillary origin. Treatment consisted of a hybrid maxillary expander anchored to palatal miniscrews and custom supragingival mandibular miniplates, placed using a fully digital workflow. Maxillary protraction was performed using a modified Alt-RAMEC protocol followed by continuous intermaxillary elastic traction for 12 months. Pre- and post-treatment cephalometric analyses were conducted. Results: A significant increase in SNA was observed (mean +6.1°, p < 0.001), indicating forward maxillary displacement. The Wits appraisal improved by 3.3 mm (p = 0.007), and the SeMax increased by 2.9 mm (p = 0.0013). No significant changes were found in the SNB or mandibular plane angle. Dentoalveolar effects were limited. Conclusions: Within the limitations of this pilot clinical study, the proposed digitally guided protocol demonstrated clinically relevant maxillary advancement with minimal dentoalveolar side effects and preserved vertical control. This relatively minimally invasive approach compared to conventional subgingival miniplates and orthognathic surgery may represent a feasible treatment option for selected late adolescent patients. Further controlled studies are required to confirm these findings. DOI: 10.3390/jcm15083070 PMID: 42074872

Mentions Semax

Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model.

1. Braz J Med Biol Res. 2026 Apr 17;59:e14744. doi: 10.1590/1414-431X2026e14744. eCollection 2026. Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model. Chege BM(1)(2), Mwangi PW(2), Githinji CG(2), Bukachi F(2). Author information: (1)School of Health Sciences, Dedan Kimathi University of Technology, Nyeri, Kenya. (2)Department of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya. The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001). Myocardial fibrosis (P<0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology. DOI: 10.1590/1414-431X2026e14744 PMCID: PMC13089955 PMID: 42018810 [Indexed for MEDLINE]

Mentions Tesamorelin

Fufang Huangbo Formula mitigates myeloproliferative neoplasms by activating p53/p21 signaling axis and inhibiting STAT3 and NF-κB signaling pathways.

1. Pharm Sci Adv. 2026 Apr 16;4:100121. doi: 10.1016/j.pscia.2026.100121. eCollection 2026 Dec. Fufang Huangbo Formula mitigates myeloproliferative neoplasms by activating p53/p21 signaling axis and inhibiting STAT3 and NF-κB signaling pathways. Liu M(1)(2)(3)(4), Li Y(1)(2)(3)(4), Qin C(1)(2)(3)(4), Wang L(1)(2)(3)(4), Guo M(1)(2)(3)(4), Wang Y(1)(2)(3)(4), Zhou Q(1)(2)(3)(4), Shi Z(5), Hao W(6), Li Y(1)(2)(3)(4), Zhao B(1)(2)(3)(4). Author information: (1)State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Jinan, Shandong, 250012, China. (2)Key Lab of Chemical Biology (MOE), Shandong University, Jinan, Shandong, 250012, China. (3)NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Shandong University, Jinan, Shandong, 250012, China. (4)Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. (5)Research Center for Traditional Chinese Medicine and Clinical Pharmacy, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, Shandong, 250012, China. (6)Department of Spine Surgery, Heze Municipal Hospital, 2888 Caozhou Road, Heze, Shandong, 274031, China. Myeloproliferative neoplasms (MPN) are hematological disorders driven by mutated hematopoietic stem cells, characterized by an increased risk of thrombosis and progression to leukemia. Patients with MPN exhibit elevated levels of inflammatory factors, which function as promoters of disease progression and transformation into acute leukemia. Fufang Huangbo formula (FHF) is a classic traditional Chinese herbal medicine widely used in the treatment of inflammation-related diseases, where it has shown considerable therapeutic efficacy. However, its potential effects on MPNs remain unclear. In this study, we demonstrate for the first time across multiple animal models that FHF significantly alleviates MPN progression, including EPO-induced polycythemia vera (PV)-like, JAK2V617F-driven PV, and MPLW515L-driven essential thrombocythemia (ET) models. FHF effectively reduced erythrocyte aggregation-induced thrombosis in PV and reversed myelofibrosis in ET. To explore the therapeutic effects, active components, and mechanisms of FHF in MPNs, we performed network pharmacology and RNA-seq analyses, with subsequent experimental validation. The results indicate that the therapeutic benefits of FHF are closely associated with cellular senescence and inflammatory responses. Validation experiments showed that FHF induces cellular senescence via activation of the p53/p21 pathway and suppresses inflammation by inhibiting the STAT3 and NF-κB signaling pathways. Our study provides scientific evidence supporting the use of FHF in the treatment of MPNs. © 2026 The Authors. DOI: 10.1016/j.pscia.2026.100121 PMCID: PMC13129468 PMID: 42078583 Conflict of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions P21

GIPR:GCGR co-agonism restores normal weight in obese rodents.

1. Mol Metab. 2026 Apr 15;108:102365. doi: 10.1016/j.molmet.2026.102365. Online ahead of print. GIPR:GCGR co-agonism restores normal weight in obese rodents. Perez-Tilve D(1), Zhang F(2), Zhang Y(2), Lohman K(1), Sorrell J(1), Vick A(3), Müller TD(4), Tschöp MH(5), DiMarchi RD(6). Author information: (1)Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. (2)Department of Chemistry, Indiana University, Bloomington, IN, USA. (3)Bluewater Biosciences, La Jolla, CA 92037, USA. (4)Institute for Diabetes and Obesity, Helmholtz Munich, Germany; German Center for Diabetes Research, DZD, Neuherberg, Germany; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University Munich, Germany. (5)Ludwig-Maximilians-University (LMU) Munich, Germany. Electronic address: tschoep@lmu.de. (6)Department of Chemistry, Indiana University, Bloomington, IN, USA. Electronic address: rdimarch@iu.edu. OBJECTIVES: Functional co- and tri-agonists at the receptors for GLP-1, GIP and glucagon effectively decrease body weight and hyperglycemia but are associated with adverse gastrointestinal effects related to GLP-1R agonism. Here we report the discovery that obesity can be reversed in the absence of a functional GLP-1R. It propelled the identification of a unimolecular GIPR:GCGR co-agonist lacking GLP-1 activity that corrects obesity in obese mice and rats. METHODS: Selective, dual, and triple sustained-action agonists at GIPR, GCGR and GLP-1R were used to assess body weight and glucose management in diet-induced obese (DIO) wildtype (WT) and GLP-1R knock-out (KO) mice. Indirect calorimetry and pair-feeding studies were used to characterize the magnitude of weight lowering specifically to suppression of food intake relative to energy expenditure. RESULTS: When used in physical co-mixture, selective GIPR agonism interacts with selective GCGR agonism to correct obesity and enhance glycemia in DIO mice. Retatrutide a balanced GLP-1R:GIPR:GCGR triagonist normalized body weight in obese GLP-1R KO mice. BWB3054, a fatty acylated GIPR:GCGR co-agonist, was identified as comparably potent as retatrutide to induce cAMP production at the mGIPR, and 4-fold reduced at mGCGR, but notably more than 100-fold diminished at mGLP-1R. Despite minimal relative GLP-1R potency, BWB3054 reduces excess body weight in obese DIO-mice to a similar degree as that observed for retatrutide in obese GLP-1R KO mice. CONCLUSIONS: Correction of obesity and glycemia in mice without employing GLP-1 agonism was demonstrated by three independent methods (GLP-1R KO with retatrutide, GIPR:GCGR physical co-agonism mixture, and GIPR:GCGR covalent co-agonist) which advocate for the prospect that the adverse GI effects commonly associated with its use might be avoided. Copyright © 2026 The Author(s). Published by Elsevier GmbH.. All rights reserved. DOI: 10.1016/j.molmet.2026.102365 PMCID: PMC13141540 PMID: 41997446 Conflict of interest statement: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.P-T. is an employee of the University of Cincinnati-College of Medicine, which has a research agreement with BWB and holds BWB stock. F.Z. and Y.Z. are employees of Indiana University, which has research and licensing agreements with BWB. K.L. and J.S. are employees of the University of Cincinnati-College of Medicine, which has a research agreement with BWB. A.V. is an employee of BWB. T.D.M. and M.H.T. are cofounders of BWB and hold BWB stock. R.D.D. is a cofounder of BWB and holds BWB stock. He is also an employee of Indiana University, which has research and licensing agreements with BWB. F.Z., M.H.T. and R.D.D. have co-invention pending that pertains to GIP:GCG coagonism.

Mentions Retatrutide