Amycretin
One molecule acting on GLP-1 and amylin receptors, tested as a weekly injection and a daily tablet; now carrying the international name zenagamtide
Amycretin, now given the international nonproprietary name zenagamtide, is an investigational Novo Nordisk drug designed as a single molecule that activates both the GLP-1 receptor and the amylin receptor. At the highest injected dose in an early trial, mean weight change was -24.3% at 36 weeks against -1.1% on placebo, and two 2026 phase 2 trials in type 2 diabetes lowered HbA1c by up to 1.7 points. It is not approved anywhere.
What is it?
GLP-1 drugs such as semaglutide and amylin analogues such as cagrilintide work through different receptors, and given together, as CagriSema, they add up. Amycretin puts both actions into one molecule. In cell assays it activated human, mouse and rat GLP-1, amylin and calcitonin receptors, and in diet-induced obese rats three weeks of treatment cut energy intake by 47% and body weight by 18% without lowering energy expenditure, while improving insulin sensitivity and fatty liver.
The first human trials, both from one research unit in San Antonio, tested two forms. In the first-in-human oral study, 144 adults with overweight or obesity took single doses, ten days of daily doses, or twelve weeks of doses escalating to two 50 mg tablets a day; 62% reported adverse events, all mild or moderate and mostly gastrointestinal. In the injectable phase 1b/2a study, 125 adults took weekly amycretin or placebo; weight fell by 24.3% at 60 mg and 22.0% at 20 mg over 36 weeks, against a 1.1% loss and a 1.9% gain on placebo.
In 2026 the drug appeared in The Lancet under its new international name, zenagamtide, in two 36-week phase 2 trials in type 2 diabetes. Weekly injections at six doses from 0.4 to 40 mg in 262 people lowered HbA1c by 0.9 to 1.7 points from a baseline of 7.8%, and daily tablets of 6, 25 or 50 mg in 186 people lowered it by 0.9 to 1.4 points. Gastrointestinal effects were the commonest, and serious adverse events occurred in 8% and 4% of those on the drug.
Set against its peers, a 2026 network meta-analysis of six trials in people without diabetes ranked high-dose injected amycretin first for weight loss, ahead of eloralintide and CagriSema, while noting more gastrointestinal effects with the high-dose amylin-based drugs. Those comparisons are indirect, across short trials of different lengths.
Amycretin is not approved anywhere. FDA's Drugs@FDA database holds no application for it and EMA's register has no entry. The only lawful way to receive it is in a clinical trial; anything sold online under either name is unregulated.
Mechanism of Action
Amycretin is built to do the work of two hormones at once: GLP-1, the gut's appetite and insulin signal, and amylin, the pancreas's fullness signal.
GLP-1 receptor agonism
Like semaglutide, it activates GLP-1 receptors, which raise insulin release when glucose is high, lower glucagon and reduce appetite; in cell assays it activated human GLP-1 receptors.
Amylin and calcitonin receptor agonism
It also activates amylin receptors and the related calcitonin receptor, the targets of cagrilintide; a 2026 review describes it acting on hindbrain satiety pathways and slowing gastric emptying.
One molecule instead of two
Combining both actions in one molecule allows a single injection or tablet, rather than co-administering two drugs as CagriSema does.
Energy balance in animals
In obese rats it cut food intake by 47% while energy expenditure was maintained, so the weight loss came from eating less rather than a fall in metabolic rate.
Published Research
These are the studies that describe amycretin, read from their PubMed abstracts: two human trials, a rodent study and a review.
Weekly injections for up to 36 weeks: 125 adults
Weekly amycretin was escalated to maintenance doses of 1.25 to 60 mg. Weight change was -24.3% against -1.1% on placebo at 60 mg and -22.0% against +1.9% at 20 mg (36 weeks), -16.2% at 5 mg (28 weeks) and -9.7% at 1.25 mg (20 weeks). Gastrointestinal events were most common, mostly mild to moderate.
First in humans, as a daily tablet: 144 adults
Single doses of 1 to 25 mg, ten days of 3 to 12 mg, and twelve-week escalations up to 2 × 50 mg daily were compared with placebo. Adverse events affected 89 of 144 participants (62%), all mild or moderate and commoner at higher doses; half were gastrointestinal, and plasma levels rose in proportion to dose.
Obese mice and rats
Amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors. In obese rats, 21 days of treatment cut energy intake by 47% and body weight by 18% with energy expenditure maintained, and improved insulin sensitivity and fatty liver.
Mechanisms and trial results reviewed
The review describes amycretin acting on hindbrain satiety pathways and slowing gastric emptying, reports weight loss of up to 13.1% on oral dosing over 12 weeks and 24.3% on injections over 36 weeks, and finds its safety profile consistent with incretin-based drugs.
Phase 2, weekly injections in type 2 diabetes: 262 adults
Six weekly doses from 0.4 to 40 mg or placebo for 36 weeks; HbA1c fell from 0.9 points (0.4 mg) to 1.7 points (40 mg), differences of 0.77 to 1.56 points from placebo. Most adverse events were gastrointestinal and mild to moderate; 8% had serious adverse events; no deaths.
Phase 2, daily tablets in type 2 diabetes: 186 adults
Oral 6, 25 or 50 mg daily or placebo for 36 weeks; HbA1c fell 0.9, 1.3 and 1.4 points (differences 0.5 to 1.09 from placebo). Gastrointestinal events affected 26%, 41% and 47% against 23% on placebo; 4% on the drug had serious adverse events.
Network meta-analysis of amylin-based drugs
Across six trials (4,642 people without diabetes), high-dose injected amycretin ranked first for weight loss against placebo (-23.95 points), ahead of high-dose eloralintide (-18.01) and CagriSema (-17.18); gastrointestinal effects were more common with high-dose amylin-based drugs.
Dosing Data
Amycretin has no approved dose. Trials escalated it gradually: weekly injections to maintenance doses of 0.4 to 60 mg, and daily tablets up to 50 mg or two 50 mg tablets.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the two human trials.
Contraindications & Cautions
Amycretin has no label. These cautions follow from how little has been tested.
Legal Status
Amycretin is an investigational drug that no regulator has approved.
Frequently Asked Questions
?What is amycretin?
An investigational Novo Nordisk drug that activates both the GLP-1 and amylin receptors with one molecule, tested as a daily tablet and a weekly injection.
?How much weight did people lose?
At 60 mg weekly, mean weight change was -24.3% at 36 weeks against -1.1% on placebo; a review reports up to 13.1% after 12 weeks of the tablet.
?Is amycretin approved?
No. FDA's Drugs@FDA database and EMA's register have no entry for it, as of September 30, 2026.
?What were the side effects?
Mostly gastrointestinal and mild to moderate; in the oral trial every adverse event was mild or moderate.
?Is amycretin the same as zenagamtide?
Yes. Zenagamtide is amycretin's international nonproprietary name, used in the 2026 phase 2 trial reports.
?Does amycretin lower blood sugar?
In 36-week phase 2 trials in type 2 diabetes, HbA1c fell by up to 1.7 points with weekly injections and up to 1.4 points with daily tablets.
?How does it compare with CagriSema?
An indirect 2026 network meta-analysis ranked high-dose amycretin above CagriSema for weight loss, but no head-to-head trial has been reported.
References
- [fda] FDA. Drugs@FDA (openFDA): no application for amycretin. Read September 30, 2026.
- [other] European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for amycretin. Read September 30, 2026.
- [pubmed] Dahl K, et al. "Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study." Lancet, 2025;406(10499):149-162. PMID: 40550231.
- [pubmed] Gasiorek A, et al. "Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial." Lancet, 2025;406(10499):135-148. PMID: 40550229.
- [pubmed] Kuhre RE, et al. "The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats." EBioMedicine, 2025;118:105862. PMID: 40706446.
- [pubmed] Fu L, et al. "Amycretin in obesity: Mechanisms, clinical efficacy, and future perspectives." Metabolism, 2026;179:156594. PMID: 41850421.
- [pubmed] Mora P, et al. "Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial." Lancet, 2026;408(10555):621-635. PMID: 42532080.
- [pubmed] Mora P, et al. "Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial." Lancet, 2026;408(10555):607-620. PMID: 42532079.
- [pubmed] Kamrul-Hasan ABM, et al. "Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis." Endocrinol Diabetes Metab, 2026;9(3):e70247. PMID: 42175595.
Sources & Citations
Every study on this page was read from its PubMed record. Regulatory status comes from FDA's Drugs@FDA database and EMA's register, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.