Amycretin
Also known as: Zenagamtide
Novo Nordisk's next-generation weight loss drug — the first single molecule that combines two appetite hormones (GLP-1 and amylin) in one shot. The same effect that CagriSema needs two drugs to achieve, amycretin does on its own. In Phase 1b/2a trials, people lost up to 22% of their body weight in 36 weeks, and a once-daily oral pill version is being developed alongside the weekly injection. Phase 3 trials began in 2026. Also known as zenagamtide.
Dosage
Fixed dose: up to 20 mg subcutaneous weekly (titrated)
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Administration
Subcutaneous injection (once weekly) and oral formulation (once daily) in development
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Effects
Weight Loss
Up to 22% body weight loss in Phase 1b/2a at 36 weeks via dual GLP-1 + amylin agonism.
Appetite Suppression
Activates two parallel satiety circuits in the brain — both GLP-1 and amylin pathways simultaneously.
Glycemic Control
Glucose-dependent insulin secretion plus amylin-mediated post-meal glucose smoothing.
Oral Bioavailability
Parallel oral formulation in development — would be a first-of-its-kind oral peptide combination.
Mechanism of Action
Amycretin is a unimolecular co-agonist that simultaneously activates both the GLP-1 receptor and the amylin (AMY) receptor — the first peptide engineered to combine these two complementary satiety pathways in a single molecule rather than as a two-drug combination. The design philosophy is to deliver the additive weight-loss benefit demonstrated by CagriSema (semaglutide + cagrilintide) without the manufacturing, dosing, and patient-acceptance complexities of co-formulating two separate drugs.
The GLP-1 component drives appetite suppression centrally through hypothalamic POMC/CART activation and NPY/AgRP inhibition, slows gastric emptying via vagal signalling, and stimulates glucose-dependent insulin secretion from pancreatic beta cells. The amylin component activates calcitonin-receptor/RAMP heterodimer complexes concentrated in the area postrema and nucleus tractus solitarius — brainstem regions outside the blood-brain barrier that form a parallel satiety circuit reducing meal size and food-seeking behaviour through neuroanatomically distinct pathways.
Because GLP-1 and amylin signal through different receptor families and target different neurons in the appetite control network, their effects are additive rather than redundant. Phase 1b/2a data showed up to 22% body weight reduction at 36 weeks for the subcutaneous form — comparable to CagriSema with a simpler one-molecule profile. A particularly notable feature is the parallel development of an oral formulation, which would be the first oral peptide combination therapy for obesity if approved. Novo Nordisk's branded development name is zenagamtide, and the molecule is positioned as the company's strategic answer to retatrutide and tirzepatide.
Regulatory Status
Not yet approved. Phase 3 clinical trials began in 2026 for both obesity and type 2 diabetes (Novo Nordisk).
Risks & Safety
Common
nausea (similar in frequency to semaglutide and tirzepatide, around 30-45% in trials), vomiting, decreased appetite, diarrhea, constipation, injection site reactions for the SC form.
Serious
pancreatitis, gallstones, dehydration-related kidney issues, possible loss of muscle mass alongside fat.
Rare
thyroid C-cell tumour signal seen in animal studies of GLP-1 class drugs, severe allergic reactions. Long-term safety still being established.
Compare Amycretin With
Research Papers
5Published: June 1, 2026
AI Summary
A 2026 review placing amycretin in the wider next-generation obesity drug landscape, noting weight reductions up to 24% via combined GLP-1 and amylin receptor activity. The authors flag plateaus, variability and rebound weight gain as ongoing limitations of incretin-based therapies.
Published: June 1, 2026
AI Summary
A focused 2026 review summarising amycretin trial data: roughly 13% weight loss over 12 weeks with the oral form and up to 24% over 36 weeks with the subcutaneous form. The safety profile so far looks similar to other incretin drugs, with mostly gastrointestinal side effects.
Published: August 1, 2025
AI Summary
The Novo Nordisk preclinical paper showing amycretin cut food intake and body weight in obese rodents while preserving energy expenditure, and improved insulin sensitivity and fatty liver markers. These animal results are what motivated the human trials.
Published: July 12, 2025
AI Summary
The first human trial of oral amycretin in 144 adults with overweight or obesity. Side effects were mostly mild-to-moderate gut symptoms and grew with dose, with no deaths; the results supported moving on to weight-loss trials.
Published: July 12, 2025
AI Summary
The phase 1b/2a trial of subcutaneous amycretin reporting average weight loss above 24% at 36 weeks, the headline finding driving interest in this drug. Side effects were largely gastrointestinal and similar to other GLP-1 drugs.
Frequently Asked Questions
What is Amycretin?
Novo Nordisk's next-generation weight loss drug — the first single molecule that combines two appetite hormones (GLP-1 and amylin) in one shot. The same effect that CagriSema needs two drugs to achieve, amycretin does on its own. In Phase 1b/2a trials, people lost up to 22% of their body weight in 36 weeks, and a once-daily oral pill version is being developed alongside the weekly injection. Phase 3 trials began in 2026. Also known as zenagamtide.
What is Amycretin used for?
Novo Nordisk's next-generation weight loss drug — the first single molecule that combines two appetite hormones (GLP-1 and amylin) in one shot. The same effect that CagriSema needs two drugs to achieve, amycretin does on its own. In Phase 1b/2a trials, people lost up to 22% of their body weight in 36 weeks, and a once-daily oral pill version is being developed alongside the weekly injection. Phase 3 trials began in 2026. Also known as zenagamtide.
What is the dosage for Amycretin?
Clinical trials (subcutaneous): doses up to 20 mg once weekly with stepwise escalation over 12-16 weeks. Oral formulation: doses up to 100 mg once daily. Dosing protocols still being optimised in Phase 3.
What are the side effects of Amycretin?
Common: nausea (similar in frequency to semaglutide and tirzepatide, around 30-45% in trials), vomiting, decreased appetite, diarrhea, constipation, injection site reactions for the SC form. Serious: pancreatitis, gallstones, dehydration-related kidney issues, possible loss of muscle mass alongside fat. Rare: thyroid C-cell tumour signal seen in animal studies of GLP-1 class drugs, severe allergic reactions. Long-term safety still being established.
How does Amycretin work?
Amycretin is a unimolecular co-agonist that simultaneously activates both the GLP-1 receptor and the amylin (AMY) receptor — the first peptide engineered to combine these two complementary satiety pathways in a single molecule rather than as a two-drug combination. The design philosophy is to deliver the additive weight-loss benefit demonstrated by CagriSema (semaglutide + cagrilintide) without the manufacturing, dosing, and patient-acceptance complexities of co-formulating two separate drugs. The GLP-1 component drives appetite suppression centrally through hypothalamic POMC/CART activation and NPY/AgRP inhibition, slows gastric emptying via vagal signalling, and stimulates glucose-dependent insulin secretion from pancreatic beta cells. The amylin component activates calcitonin-receptor/RAMP heterodimer complexes concentrated in the area postrema and nucleus tractus solitarius — brainstem regions outside the blood-brain barrier that form a parallel satiety circuit reducing meal size and food-seeking behaviour through neuroanatomically distinct pathways. Because GLP-1 and amylin signal through different receptor families and target different neurons in the appetite control network, their effects are additive rather than redundant. Phase 1b/2a data showed up to 22% body weight reduction at 36 weeks for the subcutaneous form — comparable to CagriSema with a simpler one-molecule profile. A particularly notable feature is the parallel development of an oral formulation, which would be the first oral peptide combination therapy for obesity if approved. Novo Nordisk's branded development name is zenagamtide, and the molecule is positioned as the company's strategic answer to retatrutide and tirzepatide.
How is Amycretin administered?
Amycretin is administered via subcutaneous injection (once weekly) and oral formulation (once daily) in development.
What is the half-life of Amycretin?
The half-life of Amycretin is Approximately 168 hours (7 days) for the subcutaneous formulation.
Is Amycretin legal?
Not yet approved. Phase 3 clinical trials began in 2026 for both obesity and type 2 diabetes (Novo Nordisk).
Sources. This profile is built from peer-reviewed papers indexed on PubMed, FDA-approved labelling where available, and published clinical guidelines. The 5 primary sources used are listed in the Research Papers section above, each linked to its PubMed entry. See our editorial standards for how we research and review peptide profiles.
Last reviewed. by the Peptide Reference Editorial Team. Spot an error? Email a correction.
Not medical advice. Information on this page is for educational and research reference only. Many peptides covered are not approved for human use. See our full medical disclaimer.
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