What the peptide community is saying — and living

Limosilactobacillus reuteri normalizes gut microbiota dysfunction and social deficits of rat offspring associated with prenatal exposure to stress.

Walking + GLP-1 = the ultimate fat-burning combo that doesn't wreck your body. Gentle movement meets smart science for r

Walking + GLP-1 = the ultimate fat-burning combo that doesn't wreck your body. Gentle movement meets smart science for results that actually last. Who's trying this? Want a slightly softer one instead? The secret sauce to fat loss without the burnout: daily walks paired with GLP-1. Sustainable, effective, and kind to your system. Save this for your next walk!

Mk-677

Mk-677

ATR-FTIR spectroscopy coupled with multivariate analysis for monitoring degradation and secondary structure transitions in therapeutic peptide formulations.

Reducing protein intake could increase human longevity, researchers recently suggested. That's a bad idea, for several r

Reducing protein intake could increase human longevity, researchers recently suggested. That's a bad idea, for several reasons, experts say. https://t.co/dl22JztLgj

Diabetes - 2nd update on semaglutide

Diabetes - 2nd update on semaglutide

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.

Took Peptide Critic’s Advice and Did Some Research Yesterday I posted about Ion asking a customer for additional govern

Took Peptide Critic’s Advice and Did Some Research Yesterday I posted about Ion asking a customer for additional government ID before processing an order. Peptide Critic responded with several negative comments, accused me of failing to understand the transaction and suggested that I was engagement farming. So I took the advice and did some research, on Peptide Critic. Ion is labelled a Premium Partner on Peptide Critic’s own site. The platform advertises that tier at $499 per month. Ion also has a Peptide Critic discount code and affiliate-tracked links through which the platform states it may earn commission. A commercial relationship exists, and it wasn’t disclosed while Peptide Critic publicly defended Ion and attacked my reporting. No one else complained about the post. Could this financial relationship explain why Peptide Critic was so upset by it? Perhaps the person accusing others of insufficient research should have led with that? FYI My original post about Ion remains valid. A customer was asked to provide additional ID, and questioning why a grey-market peptide vendor wanted that personal information was entirely reasonable. Peptide Critic didn't show that anything I posted was false or provide missing context that disproved it. He attacked my research and motives instead. Whatever explanation Ion may have for requesting the ID doesn't change the fact that the request was made.

Question about injection technique / possible dose loss

Question about injection technique / possible dose loss

Comparison of lifestyle, surgery, and semaglutide for weight management in endometrial cancer: a prospective observational study.

neuroplasticity is always on your side with dihexa. everybody says neuroplasticity drops to 0 when you become 25 which

neuroplasticity is always on your side with dihexa. everybody says neuroplasticity drops to 0 when you become 25 which is not true, but even then nootropics exist. you will learn faster, remember more, think quicker, recover smoothly and never burn out if you know how to use nootropics correctly. ps: dont randomly start taking nootropics thinking you are "biohacking". everything needs the correct timing, dosing, stack and potential ancillaries. be responsible about this and DYOR, your brain is on the line.

Starting to think I'm a non-responder

Starting to think I'm a non-responder

Recombinant human collagen XVII protects epidermal stem cells from blue light-induced photoaging by downregulating the Notch pathway.

1. Ann Med. 2026 Dec;58(1):2694876. doi: 10.1080/07853890.2026.2694876. Epub 2026 Jul 16. Recombinant human collagen XVII protects epidermal stem cells from blue light-induced photoaging by downregulating the Notch pathway. Wang X(1)(2)(3), Li Q(4), Yang X(1), Bai Y(1), Sui S(1), Ge G(1), Li H(1), Yang R(1). Author information: (1)Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China. (2)Department of Dermatology, Medical School of Chinese PLA, Beijing, China. (3)Department of Dermatology, Southern Medical District of Chinese PLA General Hospital, Beijing, China. (4)Medical Health Care Department, Air Force Medical Center PLA, Beijing, China. BACKGROUND: Epidermal stem cell (ESC) degeneration is closely associated with skin aging and functional deterioration. Type XVII collagen (COL17A1) critically regulates ESC polarity and epidermal homeostasis. This study investigated the protective effects of recombinant human COLXVII (rhCol17) against blue light-induced photoaging, particularly on ESC. METHODS: Blue light-induced photoaging models were established using in vitro ESCs and in vivo Sprague-Dawley rats. Transcriptomic profiling was conducted to systematically elucidate the underlying mechanisms. RESULTS: In photoaging ESCs, rhCol17 enhanced ESC viability and migratory capacity, decreased senescence cells, while suppressing ROS production and the secretion of pro-inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Furthermore, rhCol17 upregulated stem cell markers COL17A1, ITGB1, ITGA6 and P63. In photoaging rat models, rhCol17 alleviated skin dryness, reduced epidermal thickness, delayed aging, and increased the levels of COL17A1 and ITGB1. Importantly, rhCol17 treatment does not affect organ histology or biochemical parameters in rats. Mechanistically, rhCol17 could inhibit the levels of Notch1 and HES1, and senescence markers P16, P21, and P53 in photoaging ESCs and rat skin. Additionally, the ADAM10 inhibitor GI254023X slightly reduced or did not significantly alter the proportion of senescent cells or the expression levels of P16, P21, and P53 in rhCol17-treated BL-induced ESCs, whereas the Notch activator VPA significantly reversed these protective effects of rhCol17. CONCLUSION: This study demonstrates that rhCol17 counteracts blue light-induced ESC dysfunction and epidermal photoaging, suggesting therapeutic potential for photoaging intervention. DOI: 10.1080/07853890.2026.2694876 PMID: 42464532 [Indexed for MEDLINE]

Based off your experience with researching peptides, give me one piece of advice you would pass on to someone just start

Based off your experience with researching peptides, give me one piece of advice you would pass on to someone just starting to do their research. It can be about any peptide, any lesson… anything that may be helpful to someone considering them. Go 👇🏼

Storing reconstituted peptide in freezer for later user/ Peptides for field sports recovery

Storing reconstituted peptide in freezer for later user/ Peptides for field sports recovery

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).

My wife and I brought a peptide on our anniversary trip because we thought it might make the weekend more interesting.I

My wife and I brought a peptide on our anniversary trip because we thought it might make the weekend more interesting.I gave her a tiny test amount before we left, thirty minutes later, she was vomiting. was fun sitting on the bathroom floor beside near my wife while realizing the “fun peptide” has officially cancelled the night i paid, planned, and counted on to reignite us.

Has anyone had to go through PA approval with Caremark?

Has anyone had to go through PA approval with Caremark?

Effect of oral calcium carbonate on uterine contractility: a pilot randomised controlled trial.

1. J Obstet Gynaecol. 2026 Dec;46(1):2697258. doi: 10.1080/01443615.2026.2697258. Epub 2026 Jul 21. Effect of oral calcium carbonate on uterine contractility: a pilot randomised controlled trial. Bui TM(1), Nelson M(1), Rehman R(1), Stowe Ii RJ(1), Roloff KA(1), Valenzuela GJ(1). Author information: (1)Department of Women's Health, Arrowhead Regional Medical Center, Colton, California, USA. BACKGROUND: Ineffective uterine contractions contribute to labour dystocia and are a leading indication for primary caesarean delivery. Although oxytocin is the standard therapy for augmentation, prolonged exposure may result in receptor desensitisation and reduced effectiveness. Calcium is essential for myometrial contraction; however, systemic calcium homeostasis is tightly regulated, and it is unclear whether oral calcium supplementation can meaningfully influence uterine activity. This study aimed to evaluate the effect of oral calcium carbonate on uterine contractility. METHODS: We conducted a single-centre randomised controlled pilot trial at a tertiary care teaching hospital (ClinicalTrials.gov: NCT07056062). Term patients with singleton foetus in cephalic presentation and an intrauterine pressure catheter in place were randomised 1:1 to receive a single 2,000 mg oral dose of calcium carbonate or no intervention. Uterine activity was measured using Montevideo units (MVUs) at baseline and at 30-minute intervals for two hours. Secondary outcomes included contraction frequency, peak contraction pressure, labour duration, mode of delivery, oxytocin dose, and postpartum haemorrhage. Oxytocin infusion rates were held constant during the observation period. RESULTS: Eighty-nine patients were analysed (45 control; 44 intervention) with similar baseline characteristics. No statistically significant difference in baseline MVUs was observed between groups (p = 0.1825). Although absolute MVUs were higher in the intervention group at 30 minutes (p = 0.0500), this difference was not sustained at subsequent time points and was absent in change-from-baseline analyses, suggesting no clinically meaningful treatment effect. No statistically significant differences were identified in secondary outcomes. CONCLUSIONS: Oral calcium carbonate did not result in a statistically significant improvement in uterine contractility or clinical outcomes. These findings likely reflect the limited physiologic effect of oral calcium on serum calcium levels. Oral calcium carbonate appears unlikely to be an effective intervention for labour augmentation; future research should focus on strategies with more controllable mechanisms. Plain Language Summary: During labour, the uterus contracts to help the baby move through the birth canal. If contractions are too weak or poorly coordinated, labour may progress slowly, increasing the likelihood of caesarean delivery. Oxytocin is commonly used to strengthen contractions, but prolonged exposure may make the uterus less responsive over time. Calcium is an important mineral that helps muscle cells contract, including the muscles of the uterus. Because of this, we conducted a randomised clinical trial to determine whether providing calcium during labour could improve contractions. We found no meaningful differences in contraction strength or labour outcomes between patients who received calcium and those who did not. Although a difference in contraction strength was observed at one early time point, this was not sustained and did not translate into clinical benefit. These findings suggest that a single dose of oral calcium carbonate does not improve uterine contractions during labour. DOI: 10.1080/01443615.2026.2697258 PMID: 42480078 [Indexed for MEDLINE]

Tik Tok's Step-by-Step Guide to Building an “Unkillable” Peptide Business Step 1: Announce that 90% of peptide compani

Tik Tok's Step-by-Step Guide to Building an “Unkillable” Peptide Business Step 1: Announce that 90% of peptide companies will disappear within 12 months. Nothing sells mentorship quite like opening with the apocalypse. Step 2: Use cheaper payment processors instead of expensive high-risk ones. Better margins today; potential payment chaos apparently reserved for another video. Step 3: Don’t build one brand. Build an entire internet ecosystem of blogs, social accounts and recommendation pages around it. Step 4: If the lab receives a cease-and-desist, shut it down, launch a replacement and change every recommendation link. The brand is disposable; the traffic isn’t. Step 5: Update every external page so it recommends the newly reincarnated lab. Same funnel, different lab coat. Step 6: Create a peptide-tracking app offering schedules, reminders and research, plus a helpful signpost to whichever lab survived this week. Step 7: Keep the audience, SEO and app separate from the disposable storefront, allowing the marketing machine to live forever. Step 8: Call it “building for the long haul.” It’s less of a conventional business plan and more of a peptide Hydra: cut off one website and three landing pages grow back.

Quick recap of my journey so far (Jan 2026 - Aug 2026)

Quick recap of my journey so far (Jan 2026 - Aug 2026)

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

This is one of the many heavy-hitting peptides you can get prescribed by a US clinician and filled from a US compounding

This is one of the many heavy-hitting peptides you can get prescribed by a US clinician and filled from a US compounding pharmacy at https://t.co/1sx28z3Tll. Get this along with Tesamoreln, Ipamorelin, GLOW, Wolverine, BPC-157, Tirzepatide, KLOW, Epitalon and more. For human use. Not for research.

Stomach ache after eating sweets

Stomach ache after eating sweets

Role of myometrial relaxants (acute tocolytics) in intrauterine fetal resuscitation at term: why, when, what, How, and why-not?

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2698356. doi: 10.1080/14767058.2026.2698356. Epub 2026 Jul 9. Role of myometrial relaxants (acute tocolytics) in intrauterine fetal resuscitation at term: why, when, what, How, and why-not? Mappa I(1), Bolten M(2), Fieni S(3), Tahir N(4), Chandraharan E(5). Author information: (1)Department of Maternal and Child Health and Urological Sciences, Sapienza, Università di Roma, Rome, Italy. (2)Klinikum Leverkusen, Academic Teaching Hospital of Cologne University, Leverkusen, Germany. (3)Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy. (4)Department of Obstetrics & Gynaecology, Bolton NHS Foundation Trust, UK. (5)Global Academy of Medical Education & Training, London, UK. Uterine contractions cause hypoxic stress to human fetuses by repeatedly occluding maternal spiral arterioles which feed the placental bed and/or compressing the loops of the umbilical cord, interrupting blood flow through the umbilical vessels. For some fetuses, even such transient and repeated interruptions of oxygenation due to ongoing uterine contractions may increase the risk of decompensation in the "high priority" central organs (i.e. heart and the brain). The onset of anaerobic metabolism and resultant production of lactate in the central organs may lead to increased likelihood of fetal neurological injury and/or perinatal death. Therefore, an immediate relaxation of the myometrium by abolishing ongoing uterine contractions may help to rapidly restore oxygenation to fetal central organs. Such timely administration of acute tocolytics would help maintain aerobic metabolism in the high-priority fetal central organs, avoiding the onset of neurological injury and/or perinatal death. Commonly used acute tocolytics include beta-sympathomimetics, nitric oxide donors, oxytocin antagonists, which have different mechanisms of actions, and maternal side-effect profile. The indications include elimination of uterotonic-induced excessive uterine contractions to facilitate normalization of the fetal heart rate so as to allow continuation of labor in anticipation of vaginal birth and for rapidly improving the fetal condition immediately prior to an emergency cesarean section. The latter includes umbilical cord prolapse or chronic hypoxia when a delay in birth is anticipated. This review addresses the indications for acute tocolytics (why), the recommended timing of administration (when), ideal tocolytic (what), route of administration (how), side effects and contraindications (why-not). Based on current evidence, and pharmacokinetics, 250 mcg of subcutaneous terbutaline (or another beta-sympathomimetic such as intravenous fenoterol) is the recommended first line tocolytic, unless there are specific maternal contraindications. In the absence of maternal hypotension, 100 mg of intravenous glyceryl trinitrate (GTN) may be administered as an alternative. Acute tocolytics are not recommended to treat myometrial irritability observed in chorioamnionitis or in acute feto-maternal hemorrhage. DOI: 10.1080/14767058.2026.2698356 PMID: 42425549 [Indexed for MEDLINE]

Good thing I haven’t started Ipamorelin. I was waiting on these results. What I am going to do is a washout period so

Good thing I haven’t started Ipamorelin. I was waiting on these results. What I am going to do is a washout period so stop CJC completely, go back to maintenance calories, stop fasting, and then re-test again. Try to isolate if the issue is with calorie restriction or something else.

Mounjaro

Mounjaro

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

When the “Responsible” Age Gate Becomes Evidence Most RUO vendors probably assume that a 21+ age gate is the responsibl

When the “Responsible” Age Gate Becomes Evidence Most RUO vendors probably assume that a 21+ age gate is the responsible thing to add. Keep minors away, restrict access and provide another layer between an RUO website and the general public. Some attorneys have also recommended age gates and account creation for precisely that reason. Eli Lilly has now cited 21+ age gates in three of its four lawsuits against “research use only” peptide sellers. In its complaint against Lone Star Peptide Co., Lilly specifically lists the age-verification gate among the practices it says demonstrate that retatrutide was being marketed and sold for human consumption. The other evidence, weight-loss advertising, dosing information and reconstitution guidance, is hardly surprising. Everyone already knows that openly telling customers what a product does and how to use it undermines an RUO disclaimer. The age gate is the interesting part because it was presumably added to do the opposite. Lilly doesn't explain why it considers the age gate relevant. It simply includes it among the practices that, taken together, it says show the products were intended for human consumption. That makes its inclusion particularly notable: a restriction vendors may regard as a responsible safeguard is being used in the opposite direction, without Lilly explaining what the gate itself proves. An age gate may still be a responsible precaution, but vendors should not assume it provides legal protection. Lilly has taken the very safeguard that was supposed to help them and placed it inside the paragraph alleging human consumption.

Side effect??

Side effect??