Amycretin (Zenagamtide)
Also known as: Zenagamtide, Amycretin
Unimolecular GLP-1 receptor and amylin receptor (AMYR) / calcitonin receptor (CTR) co-agonist peptide
What it is
Amycretin (now also called zenagamtide) is a novel, single-molecule co-agonist that simultaneously activates GLP-1 receptors, amylin receptors (AMYR), and calcitonin receptors (CTR) (PMID 42532080; PMID 42532079; PMID 40550231). Its dual/triple receptor engagement synergistically engages hindbrain-mediated satiety pathways and delays gastric emptying, thereby reducing food intake and promoting weight loss. In preclinical studies, amycretin activated human, mouse, and rat GLP-1, amylin, and calcitonin receptors in cell-based systems, targeted key brain areas regulating food intake, reduced total energy intake, lowered body weight while maintaining energy expenditure, improved insulin sensitivity, and improved histological hallmarks of metabolic dysfunction-associated steatotic liver disease (MASLD) in diet-induced obese rats. The amylin receptor component acts centrally to induce satiety, suppress prandial glucagon release, and modulate gastric motility, complementing the insulinotropic and appetite-suppressing actions of GLP-1 receptor agonism (PMID 41747885; PMID 41344603).
Class: Unimolecular GLP-1 receptor and amylin receptor (AMYR) / calcitonin receptor (CTR) co-agonist peptide
What it's studied for
- Weight loss / obesity management Mixed
- Estimated mean bodyweight change from baseline vs placebo: Part B (60 mg, 36 weeks): -24.3% vs -1.1%; Part C (20 mg, 36 weeks): -22.0% vs 1.9%; Part D (5 mg, 28 weeks): -16.2% vs 2.3%; Part E (1.25 mg, 20 weeks): -9.7% vs 2.0% (all p<0.001). PMID 40550231 Dahl K et al. Lancet (2025). Phase 1b/2a RCT, subcutaneous amycretin in adults with overweight or obesity.
- Oral amycretin appeared safe and tolerable; exploratory pharmacodynamic endpoints included bodyweight change. Results supported further investigation of weight loss properties. PMID 40550229 Gasiorek A et al. Lancet (2025). Phase 1 first-in-human RCT, oral amycretin in adults with overweight or obesity.
- High-dose subcutaneous amycretin produced the largest reduction in percent body weight vs placebo (mean difference -23.95%; P score 1.00) among agents studied, exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). GI AEs were more common with high-dose amycretin. PMID 42175595 Kamrul-Hasan ABM et al. Endocrinology, Diabetes & Metabolism (2026). Network meta-analysis of amylin-based therapies in adults with overweight/obesity without diabetes.
- Placebo-subtracted weight reduction of -23.9% (95% CI: -29.3% to -18.5%) observed with amycretin, numerically greater than all approved agents reviewed. PMID 42673585 Moiz A et al. Annals of Internal Medicine (2026). Updated systematic review of GLP-1 RAs and co-agonists for weight loss in adults without diabetes.
- Review summarizes weight reduction of up to 13.1% with oral administration (12 weeks) and 24.3% with subcutaneous delivery (36 weeks). PMID 41850421 Fu L et al. Metabolism (2026). Review of amycretin mechanisms and clinical efficacy.
- Glycemic control / type 2 diabetes Human RCT
- At week 36, estimated change in HbA1c ranged from -0.9% (zenagamtide 0.4 mg; ETD vs placebo -0.77%, p=0.0021) to -1.7% (zenagamtide 40 mg; ETD -1.56%, p<0.0001). All doses produced clinically meaningful, statistically significant improvements vs placebo. PMID 42532080 Mora P et al. Lancet (2026). Phase 2 RCT, once-weekly subcutaneous zenagamtide in adults with type 2 diabetes.
- At week 36, estimated mean change in HbA1c: -0.9% with 6 mg (ETD -0.5%, p=0.033), -1.3% with 25 mg (ETD -0.99%, p=0.0001), -1.4% with 50 mg (ETD -1.09%, p<0.0001). Safety consistent with GLP-1 and amylin receptor agonists. PMID 42532079 Mora P et al. Lancet (2026). Phase 2 RCT, once-daily oral zenagamtide in adults with type 2 diabetes.
- Metabolic dysfunction-associated steatotic liver disease (MASLD) Animal studies only
- Amycretin improved histological hallmarks of MASLD, primarily by reducing steatosis, in diet-induced obese rats. PMID 40706446 Kuhre RE et al. EBioMedicine (2025). Preclinical study in diet-induced obese mice and rats.
- Insulin resistance / improvement of insulin sensitivity Animal studies only
- Insulin sensitivity improved significantly with amycretin administration in DIO rats compared with vehicle controls, shown by higher glucose infusion rates during a hyperinsulinaemic euglycemic clamp. PMID 40706446 Kuhre RE et al. EBioMedicine (2025). Preclinical study in diet-induced obese rats.
- Post-transplant diabetes mellitus (investigational mention) In vitro only
- Amycretin is mentioned among hypoglycemic drugs still in clinical trials as a potential treatment option for post-transplant diabetes mellitus; no efficacy data in transplant populations provided. PMID 39204092 Rudzki G et al. Pharmaceuticals (Basel) (2024). Review of managing post-transplant diabetes mellitus.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Subcutaneous injection, once weekly | Part B: once-weekly escalation from 0.3 mg to 60 mg (maintenance); Part C: 0.3 mg to 20 mg (maintenance); Part D: 0.3 mg to 5 mg (maintenance); Part E: 0.3 mg to 1.25 mg (maintenance) | Part B/C: 36 weeks; Part D: 28 weeks; Part E: 20 weeks | human | Research PMID 40550231 |
| Oral (tablet), once daily | Part A: single ascending doses of oral amycretin 1 mg, 3 mg, 6 mg, 12 mg, 18 mg (12+6 mg), or 25 mg; Part B: multiple ascending doses 3 mg, 6 mg, or 12 mg once daily; Part C/D: titration from 3–6 mg up to 50 mg or 2×50 mg or 2×25 mg once daily | Part A: single dose (1 day); Part B: 10 days; Part C/D: 12 weeks | human | Research PMID 40550229 |
| Subcutaneous injection, once weekly | Once-weekly subcutaneous zenagamtide: 0.4, 1.5, 5, 10, 20, or 40 mg (starting dose 0.2 mg with escalations every 4 weeks) | 36 weeks | human | Research PMID 42532080 |
| Oral (tablet), once daily | Once-daily oral zenagamtide: 6, 25, or 50 mg (starting dose 1.5 mg with escalations every 4 weeks) | 36 weeks | human | Research PMID 42532079 |
| Not explicitly stated in abstract | Not explicitly stated in abstract (dose characterized in diet-induced obese rats over 21 days) | 21 days | animal | Research PMID 40706446 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Gastrointestinal adverse events (nausea, vomiting, constipation, and other GI symptoms) were the most common treatment-emergent adverse events across all clinical trials, were mostly mild to moderate in severity, increased with dose, and generally resolved during continued use. PMID 40550231
- Gastrointestinal adverse events (occurring in 26–47% of oral zenagamtide-treated participants across dose groups vs 23% with placebo) were the most common adverse events in the oral phase 2 trial; serious adverse events occurred in 4% of zenagamtide-treated participants. PMID 42532079
- Serious adverse events reported in 8% of subcutaneous zenagamtide-treated participants (distributed across all dose groups) in the phase 2 trial; no deaths occurred. PMID 42532080
- In a network meta-analysis, high-dose subcutaneous amycretin and oral amycretin were associated with numerically greater rates of GI AEs, nausea, vomiting, and constipation compared with placebo and some other amylin-based therapies. PMID 42175595
- All treatment-emergent adverse events in the phase 1 first-in-human trial were mild or moderate in severity; 364 events were reported in 89 (62%) of 144 participants, with GI events accounting for 49% of all events. No deaths reported. PMID 40550229
- Gastrointestinal side effects, especially nausea, similar to those reported for GLP-1R agonists, are commonplace during initiation and up-titration of amylin analogues including amycretin, but mostly resolve during continued use. PMID 41747885
Contraindications
- Phase 2 trials excluded adults outside the age range of 18–75 years, those with HbA1c outside 7.0–10.0%, and those with BMI outside 23.0 to <50.0 kg/m²; populations outside these parameters have not been studied in reviewed trials. PMID 42532080
- Phase 1b/2a subcutaneous trial excluded individuals outside 18–55 years of age and BMI outside 27.0–39.9 kg/m²; no formal contraindications beyond trial eligibility criteria are stated in the reviewed abstracts. PMID 40550231
Frequently asked
What is amycretin and how does it work?
Amycretin (also now called zenagamtide) is a novel, single-molecule co-agonist that simultaneously activates GLP-1 receptors, amylin receptors (AMYR), and calcitonin receptors (CTR) (PMID 42532080; PMID 42532079). It works by synergistically engaging hindbrain-mediated satiety pathways and delaying gastric emptying to reduce food intake and promote weight loss. In preclinical studies in rats, it reduced total energy intake by 47% and lowered body weight by 18% over 21 days compared to vehicle.
How much weight loss has been seen with amycretin in clinical trials?
In a phase 1b/2a randomised controlled study in people with overweight or obesity (n=101 on amycretin), estimated mean bodyweight change from baseline versus placebo was: -24.3% vs -1.1% at 36 weeks (subcutaneous 60 mg), -22.0% vs +1.9% at 36 weeks (subcutaneous 20 mg), -16.2% vs +2.3% at 28 weeks (subcutaneous 5 mg), and -9.7% vs +2.0% at 20 weeks (subcutaneous 1.25 mg). A network meta-analysis reported a placebo-subtracted reduction of -23.95% for high-dose subcutaneous amycretin. A systematic review reported placebo-subtracted weight reduction of -23.9% (95% CI: -29.3% to -18.5%). Oral amycretin achieved up to 13.1% weight loss in 85 days in phase 1 studies. These are trial results; individual outcomes vary.
What dose of amycretin should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: In phase 1b/2a trials, subcutaneous amycretin was escalated from 0.3 mg up to maintenance doses of 1.25–60 mg once weekly over treatment durations of 20–36 weeks. In phase 2 trials (as zenagamtide), subcutaneous doses of 0.4–40 mg once weekly and oral doses of 6–50 mg once daily were investigated (PMID 42532080; PMID 42532079). All dosing was conducted under clinical trial conditions with medical supervision.
Is amycretin FDA-approved?
The reviewed published literature does not explicitly state the current FDA, Health Canada, or WADA regulatory status of amycretin/zenagamtide. Based on the abstracts reviewed, amycretin has been studied in phase 1 and phase 2 clinical trials only (PMID 40550229; PMID 40550231; PMID 42532080; PMID 42532079). Please consult a licensed provider or check official regulatory authority websites for current approval status — requires manual verification.
What are the side effects of amycretin?
In clinical trials, the most common adverse events were gastrointestinal in nature (nausea, vomiting, constipation), were mostly mild to moderate in severity, and increased in frequency with higher doses (PMID 40550231; PMID 40550229). In the oral phase 2 trial, GI adverse events occurred in 26–47% of zenagamtide-treated participants versus 23% with placebo. Serious adverse events were reported in approximately 4–8% of treated participants across trials, with no deaths (PMID 42532079; PMID 42532080). GI side effects were generally similar to those seen with GLP-1 and amylin receptor agonists and mostly resolved with continued use.
Can I use amycretin for type 2 diabetes?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. Research context: In phase 2 trials (as zenagamtide), once-weekly subcutaneous dosing (0.4–40 mg) produced statistically significant reductions in HbA1c of -0.9% to -1.7% vs placebo at 36 weeks in adults with type 2 diabetes. Once-daily oral zenagamtide (6–50 mg) produced HbA1c reductions of -0.9% to -1.4% vs placebo at 36 weeks in a similar population. These are phase 2 trial results; the compound is investigational and not approved for clinical use per the reviewed literature.
Can I stack amycretin with another peptide or SGLT2 inhibitor?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: In the phase 2 trials, participants were permitted to be on stable doses of metformin with or without an SGLT2 inhibitor as background therapy (PMID 42532080; PMID 42532079). One review discusses the strategic potential of combining amycretin with SGLT2 inhibitors to optimize cardio-renal outcomes, but notes this is a theoretical framework without confirmed clinical trial data as of the review. No head-to-head stacking studies with other peptides were identified in the reviewed abstracts.
Where can I buy amycretin?
I don't recommend vendors or sources. Please consult a licensed provider. Note: per the reviewed published literature, amycretin/zenagamtide is an investigational compound studied in clinical trials funded by Novo Nordisk (PMID 40550231; PMID 40550229); it does not appear to be approved for commercial sale.
How does amycretin compare to semaglutide or tirzepatide?
Direct head-to-head RCTs comparing amycretin to semaglutide or tirzepatide are not present in the reviewed abstracts. Indirect comparison data from a network meta-analysis showed high-dose subcutaneous amycretin produced the largest percent body weight reduction (-23.95% vs placebo; P score 1.00) among agents studied, exceeding semaglutide 2.4 mg (-11.45%) and liraglutide 3.0 mg (-6.4%). A systematic review reported amycretin placebo-subtracted weight loss of -23.9% versus tirzepatide at -19.0% and subcutaneous semaglutide at -14.8%. These are indirect comparisons with important methodological limitations.
Is there data on amycretin's effects on the heart or cardiovascular outcomes?
I don't have reliable study data on that specific question from the reviewed abstracts. One review discussed the known or predicted cardiac effects of GLP-1 co-agonists generally and noted that preclinical cardiac studies in mice may be misleading for predicting human cardiac effects, but no specific cardiovascular outcome data for amycretin in humans is provided in the reviewed abstracts. I won't guess — please consult a licensed provider or peer-reviewed literature directly.
References
- [1] PMID 40550231 — Estimated mean bodyweight change from baseline vs placebo: Part B (60 mg, 36 weeks): -24.3% vs -1.1%; Part C (20 mg, 36 weeks): -22.0% vs 1.9%; Part D (5 mg, 28
- [2] PMID 40550229 — Oral amycretin appeared safe and tolerable; exploratory pharmacodynamic endpoints included bodyweight change. Results supported further investigation of weight
- [3] PMID 42175595 — High-dose subcutaneous amycretin produced the largest reduction in percent body weight vs placebo (mean difference -23.95%; P score 1.00) among agents studied,
- [4] PMID 42673585 — Placebo-subtracted weight reduction of -23.9% (95% CI: -29.3% to -18.5%) observed with amycretin, numerically greater than all approved agents reviewed.
- [5] PMID 41850421 — Review summarizes weight reduction of up to 13.1% with oral administration (12 weeks) and 24.3% with subcutaneous delivery (36 weeks).
- [6] PMID 42532080 — At week 36, estimated change in HbA1c ranged from -0.9% (zenagamtide 0.4 mg; ETD vs placebo -0.77%, p=0.0021) to -1.7% (zenagamtide 40 mg; ETD -1.56%, p<0.0001)
- [7] PMID 42532079 — At week 36, estimated mean change in HbA1c: -0.9% with 6 mg (ETD -0.5%, p=0.033), -1.3% with 25 mg (ETD -0.99%, p=0.0001), -1.4% with 50 mg (ETD -1.09%, p<0.000
- [8] PMID 40706446 — Amycretin improved histological hallmarks of MASLD, primarily by reducing steatosis, in diet-induced obese rats.
- [9] PMID 39204092 — Amycretin is mentioned among hypoglycemic drugs still in clinical trials as a potential treatment option for post-transplant diabetes mellitus; no efficacy data
- [10] PMID 41747885 — Gastrointestinal side effects, especially nausea, similar to those reported for GLP-1R agonists, are commonplace during initiation and up-titration of amylin an
- [11] PMID 41344603 — in-prose reference
- [12] PMID 42768195 — in-prose reference