Amycretin

Dosing from the Literature

Published for fat loss: weekly injections stepped up from 0.3 mg to 1.25, 5, 20 or 60 mg over 20 to 36 weeks, and daily tablets up to 2 × 50 mg for 12 weeks, in early trials. Not published: the phase 3 doses; the AMAZE records list dose levels, not amounts.

No dose of amycretin is approved. The table records the trial doses as the papers and registry records give them. They are trial doses, not recommendations; in the multi-week trials the dose started low and was stepped up.

What It Is

Amycretin is an experimental drug from Novo Nordisk: one peptide built to act on two hormone systems at once, the GLP-1 receptor and the amylin receptors (Kuhre et al., 2025). Its code name is NNC0487-0111. Its proposed international nonproprietary name is zenagamtide, published by the WHO in Proposed INN List 133 (WHO, 2025); Novo Nordisk’s full-year 2025 report calls it “zenagamtide (previously amycretin)” (Novo Nordisk, February 3, 2026). It is being developed as a once-weekly injection and a once-daily tablet, for adults with overweight or obesity and for type 2 diabetes (Novo Nordisk, November 25, 2025).

The molecule is a 68-amino-acid peptide, formula C343H550N94O116, average molecular weight 7847 Da. A modified GLP-1 sequence is joined by a short linker of four glycines and a glutamic acid to a calcitonin-based sequence that acts on amylin receptors. A C18 fatty diacid side chain lets it bind albumin reversibly in the blood, which gives it a long half-life, and 2-aminoisobutyric acid near the start of the GLP-1 part protects it from the enzyme DPP-4 (Kuhre et al., 2025; WHO, 2025). Novo Nordisk’s scientists write that they designed it to match CagriSema, the combination of cagrilintide and semaglutide, in potency at both receptor types in cell tests (Kuhre et al., 2025).

The first-in-human trial, of tablets, enrolled its first participants in May 2022 (Gasiorek et al., 2025). Two early trials were published in The Lancet in 2025 (Gasiorek et al., 2025; Dahl et al., 2025), and the phase 2 diabetes trial, as two papers (injection and tablet), in The Lancet in 2026 (Mora et al., 2026). In June 2025 Novo Nordisk said it would take both the injection and the tablet into phase 3 for weight management, after end-of-phase-2 feedback from regulators (Novo Nordisk, June 12, 2025). The AMAZE phase 3 programme started in the first quarter of 2026 (Novo Nordisk, May 6, 2026). ClinicalTrials.gov lists 28 trials of the compound, 14 of them phase 3 (searched September 29, 2026). It is not FDA-approved.

What has not been published: any phase 3 result, any trial longer than 36 weeks, any head-to-head comparison with another weight-loss drug, and the results of five completed phase 1 trials (listed under Human Data). A PubMed search for amycretin, zenagamtide or NNC0487-0111 on September 29, 2026 returned 26 records; six report original studies of the compound, five in people and one in mice and rats.

Mechanism of Action

The receptor and animal work below comes from one paper by Novo Nordisk’s scientists (Kuhre et al., 2025); the human half-life comes from the kidney study (Oldenburg et al., 2026).

• GLP-1 receptor — In cell assays amycretin activated the human GLP-1 receptor with a potency comparable to semaglutide’s (EC50 1.1 pM vs 1.2 pM) (Kuhre et al., 2025).
• Amylin receptors (AMY1, AMY2, AMY3) and the calcitonin receptor — It activated all three human amylin receptors and the human calcitonin receptor, with negligible activity at the CGRP and adrenomedullin receptors; it also activated the mouse and rat forms (Kuhre et al., 2025). The phase 2 papers describe it as an agonist of GLP-1, amylin and calcitonin receptors (Mora et al., 2026).
• Albumin binding (C18 diacid side chain) — The fatty side chain binds albumin reversibly and gives a long half-life (Kuhre et al., 2025). In monkeys the half-life was about 29 hours (Kuhre et al., 2025). In people given one 0.3 mg injection, the geometric mean half-life was 88.1 hours with normal kidney function and 94.0 to 112.8 hours with impaired kidney function, with a median time to peak of about 48 hours (36 hours in people on dialysis) (Oldenburg et al., 2026).
• Brain regions that regulate eating (mice) — A fluorescent version injected into mice reached four circumventricular organs (area postrema, median eminence, vascular organ of the lamina terminalis, subfornical organ) and three regions behind the blood–brain barrier: the arcuate nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus. Semaglutide reached the same regions (Kuhre et al., 2025).
• Food intake and energy expenditure (rats) — In obese rats, amycretin cut energy intake by 47.4% over three weeks. Rats fed less to match its weight loss burned 13.6% less energy than the amycretin group, while the amycretin group’s energy expenditure did not differ from untreated rats. The authors read this as amycretin preventing the downregulation of energy expenditure known as metabolic adaptation, in rats (Kuhre et al., 2025).
• Insulin sensitivity (rats) — After 35 days, treated obese rats needed about three times the glucose infusion rate of untreated rats to hold blood sugar steady in a hyperinsulinaemic clamp, and took up significantly more glucose. The authors write that it is unknown whether this comes from the weight loss or from other actions of the drug (Kuhre et al., 2025).

What the Research Shows

• Weight in obese mice and rats — Over 21 days, obese mice lost 15.8% (2 nmol/kg) and 21.3% (10 nmol/kg) of body weight relative to untreated mice; obese rats lost 18.3% over three weeks relative to untreated rats. In the rats about 70% of the loss was fat mass and about 30% lean mass; EchoMRI measures the latter as fat-free mass, which includes skin, bone and organs as well as muscle (Kuhre et al., 2025).
• Fatty liver (mice) — In a mouse model of fatty liver disease, 12 weeks of amycretin gave a 2-point or larger improvement in the MASLD activity score in 55.6% (10 nmol/kg) and 64.7% (30 nmol/kg) of mice, against 44.4% on semaglutide and none on vehicle, mostly through less fat in the liver (Kuhre et al., 2025).
• Weight in people with overweight or obesity (injection) — In the phase 1b/2a trial, estimated weight change was −22.0% on 20 mg against +1.9% on placebo at 36 weeks, and −24.3% against −1.1% in the group stepped up to 60 mg (Dahl et al., 2025). Two later papers note that weight loss had not levelled off at 36 weeks (Oldenburg et al., 2026; Alhazmi & le Roux, 2026).
• Weight in people with overweight or obesity (tablet) — In the phase 1 trial, daily tablets were followed by weight loss of up to 13.1% at 12 weeks on 2 × 50 mg, against 1.2% on placebo (Oldenburg et al., 2026, reporting Gasiorek et al., 2025).
• Blood sugar in type 2 diabetes — After 36 weeks, HbA1c fell by 0.9% to 1.7% on weekly injections, by dose, and by 0.9% to 1.4% on daily tablets, all significantly more than on placebo (Mora et al., 2026). Novo Nordisk’s announcement of the same trial reported weight loss of up to 14.5% on injections against 2.6% on placebo, and up to 10.1% on tablets against 2.5%, estimated as if everyone had stayed on treatment; the published abstracts give the HbA1c results, not the weight results (Novo Nordisk, November 25, 2025).
• How it compares, across trials — A 2026 network meta-analysis of six trials in people without diabetes ranked high-dose injected amycretin first for weight loss (mean difference from placebo −23.95%), ahead of high-dose eloralintide (−18.01%), high-dose CagriSema (−17.18%) and semaglutide 2.4 mg (−11.45%); its authors call the data sparse and of low certainty, and the findings preliminary (Kamrul-Hasan et al., 2026). A 2026 systematic review lists placebo-subtracted weight loss of 23.9% with amycretin and 22.1% with retatrutide (Moiz et al., 2026). These compare separate trials; no trial has put amycretin against another drug head to head and reported.

Human Data

Five published trial reports from four registered trials, 759 people, all funded by Novo Nordisk:

• First-in-human, oral (phase 1; Gasiorek et al., 2025; NCT05369390) — Randomized, double-blind and placebo-controlled, at one research unit in San Antonio, TX: 144 adults with overweight or obesity, enrolled between May 2022 and January 2024, in single-dose, 10-day and 12-week parts. There were 364 adverse events in 89 (62%) of 144 participants, all mild or moderate and more frequent at higher doses; 180 (49%) of the events were gastrointestinal. No deaths were reported. Blood levels rose in proportion to dose. The abstract does not give the weight results; a later paper reports up to 13.1% weight loss at 12 weeks on 2 × 50 mg against 1.2% on placebo (Oldenburg et al., 2026).
• Weekly injection, overweight or obesity (phase 1b/2a; Dahl et al., 2025; NCT06064006) — Randomized and placebo-controlled, participants and investigators masked, at one site in San Antonio: 125 adults aged 18–55, randomly allocated between September 2023 and April 2024 (101 to amycretin, 24 to placebo). Estimated weight change: −9.7% on 1.25 mg at week 20 (placebo +2.0%), −16.2% on 5 mg at week 28 (+2.3%), −22.0% on 20 mg at week 36 (+1.9%) and −24.3% in the group stepped up to 60 mg at week 36 (−1.1%). The primary endpoint was adverse events: the most common were gastrointestinal, and most were mild to moderate and resolved by the end of the study. Many participants withdrew, a high proportion for reasons unrelated to adverse events.
• Weekly injection, type 2 diabetes (phase 2; Mora et al., 2026; NCT06542874) — Randomized, double-blind and placebo-controlled, at 83 sites in 11 countries: 262 adults on metformin, with or without an SGLT2 inhibitor, given 0.4 to 40 mg or placebo for 36 weeks. From a baseline HbA1c of 7.8%, HbA1c fell by 0.9% on 0.4 mg (0.77 points more than placebo) to 1.7% on 40 mg (1.56 points more). Most adverse events were gastrointestinal and mild to moderate; 21 (8%) of 261 participants had serious adverse events, three of them on placebo. No deaths occurred.
• Daily tablet, type 2 diabetes (phase 2; Mora et al., 2026; NCT06542874) — The same trial’s oral arm: 186 adults given 6, 25 or 50 mg or placebo for 36 weeks. HbA1c fell by 0.9%, 1.3% and 1.4% (0.5, 0.99 and 1.09 points more than placebo). Serious adverse events were reported in seven participants on the drug and none on placebo. No deaths occurred.
• Kidney function (phase 1; Oldenburg et al., 2026; NCT06559527) — Open-label, single dose of 0.3 mg in 42 adults at one centre in Berlin, 14 with normal kidney function and 7 in each of four impairment groups, up to kidney failure on dialysis. Exposure was up to 35% higher with impaired function, which the authors judged not clinically relevant; they conclude that no dose adjustment is warranted.

Completed, no results. Five completed phase 1 trials have neither posted results nor a linked publication on ClinicalTrials.gov (checked September 29, 2026): tablets in Japanese men with obesity (NCT06049329), an oral contraceptive and stomach-emptying study (NCT06461039), oral formulations and food (NCT06478563), tablets in Chinese adults (NCT06820476) and injections in Chinese adults (NCT07121153).

Phase 3, registered. ClinicalTrials.gov lists 14 phase 3 trials (searched September 29, 2026). All but AMAZE 9 give weekly injections; AMAZE 9 gives daily tablets. None has reported.

The registry lists AMAZE 8 and AMAZE 13 as not yet recruiting and AMAZE 12 as active, not recruiting; Novo Nordisk reported AMAZE 8 and HF-POLARIS as initiated in its first-half 2026 report (Novo Nordisk, August 4, 2026). Five phase 1 trials are also open or planned: on appetite and meals (NCT07508020), insulin sensitivity in type 2 diabetes (NCT07535307), liver impairment (NCT07587710), energy use after weight loss (NCT07757087), and meal timing and water volume with tablets (NCT07815067).

Reconstitution & Storage

Nothing in the documents read for this page is a powder to mix. In the trials amycretin is given by pen or as tablets: PDS290 pre-filled pen-injectors in the phase 3 records, a NovoPen 4 in the kidney study, and tablets for the oral form (ClinicalTrials.gov). No document read for this page describes amycretin sold as a freeze-dried powder, so there is no documented vial size to build a mixing table on.

• Injection sites in the documents — The phase 3 records give the injection into the thigh, abdomen or upper arm (ClinicalTrials.gov, NCT07339423).
• Tablets in the documents — A registered study of meal timing and water volume gives the tablet in the morning, fasted (ClinicalTrials.gov, NCT07815067).
• Storage — No storage conditions for amycretin pens or tablets appear in the documents read for this page.

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Side Effects & Risks

What the published trials recorded:

• Gastrointestinal effects — The most common adverse events in every published trial, mostly mild to moderate (Dahl et al., 2025; Gasiorek et al., 2025; Mora et al., 2026; Oldenburg et al., 2026). In the oral phase 1, gastrointestinal events made up 180 (49%) of 364 adverse events and occurred in 72 (81%) of the 89 participants who had any adverse event (Gasiorek et al., 2025). In the tablet diabetes trial they affected 14 (26%) of 54 participants on 6 mg, 21 (41%) of 51 on 25 mg and 24 (47%) of 51 on 50 mg, against 7 (23%) of 30 on placebo (Mora et al., 2026). A 2026 review’s table of the two early trials gives nausea at 50% to 82% and vomiting at 25% to 53% (Alhazmi & le Roux, 2026).
• After a single small dose — In the kidney study, one 0.3 mg injection was followed by adverse events in 30 (71.4%) of 42 participants, all mild or moderate and none serious: decreased appetite in 17 (40.5%), nausea in 7 (16.7%) and vomiting in 7 (16.7%) (Oldenburg et al., 2026).
• Serious adverse events — In the injection diabetes trial, 21 (8%) of 261 participants, three of them on placebo; in the tablet diabetes trial, seven participants on the drug and none on placebo (Mora et al., 2026). No deaths are reported in the oral phase 1, the two diabetes papers or the kidney study.
• Stopping treatment — Many participants withdrew from the injection trial, a high proportion for reasons unrelated to adverse events (Dahl et al., 2025). The 2026 review’s table gives discontinuation for adverse events ranging from 0% to 35% in the two early trials (Alhazmi & le Roux, 2026).
• Kidney impairment — Exposure after one dose was up to 35% higher with impaired kidney function; the authors judged this not clinically relevant and identified no safety or tolerability issues, in one single-dose study (Oldenburg et al., 2026).
• Drug interactions — Not reported. A completed phase 1 trial of amycretin with an oral contraceptive, which also measured stomach emptying, has no posted or published results (ClinicalTrials.gov, NCT06461039).
• What is in a vial — The documents read for this page describe only Novo Nordisk’s trial supplies. None describes amycretin sold outside the trials, or any analysis of such a product.
• WADA — Amycretin is not named on the 2026 Prohibited List. Section S0 prohibits at all times any pharmacological substance not addressed by the List’s other sections and with no current approval by any governmental regulatory health authority for human therapeutic use, and gives drugs under clinical development as an example (Prohibited List 2026).

Bloodwork & Monitoring

No monitoring guidance for amycretin has been published, and it has no label. What the published trials measured:

• HbA1c and blood glucose — The primary outcome of the phase 2 diabetes trial was HbA1c at 36 weeks (Mora et al., 2026); the oral phase 1 tracked fasting plasma glucose (Gasiorek et al., 2025).
• Body weight — A secondary endpoint of the injection trial and of the diabetes trial, and exploratory in the oral phase 1 (Dahl et al., 2025; Novo Nordisk, November 25, 2025; Gasiorek et al., 2025).
• Kidney function — The kidney study grouped participants by eGFR, from the CKD-EPI 2021 creatinine equation, and found no clinically relevant change in exposure (Oldenburg et al., 2026).
• Laboratory tests, ECG and vital signs — No clinically relevant findings after a single dose in the kidney study (Oldenburg et al., 2026).
• Which tests fit a given person — A question for a licensed healthcare provider. This page can’t answer it.

Commonly Stacked With

No document read for this page shows amycretin combined with another peptide, by users or in a study. What the trials combined it with is background treatment, recorded here as the documents give it:

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Legal Status

Related Compounds

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References

1. Gasiorek A, Heydorn A, Gabery S, Hjerpsted JB, Kirkeby K, Kruse T, Petersen SB, Toubro S, Vegge A, Key C. 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.
2. Dahl K, Toubro S, Dey S, Duque do Vale R, Flint A, Gasiorek A, Heydorn A, Jastreboff AM, Key C, Petersen SB, Vegge A, Adelborg K. 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.
3. Kuhre RE, Ballarín-González B, Brand CL, Glendorf T, Madsen KG, Hjøllund KR, Hogendorf WFJ, Ipsen DH, Lundh S, Kruse T, Petersen SB, Secher A, Vegge A, Raun K. 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. (Structure, receptor potencies, animal pharmacokinetics and the rodent studies.)
4. Oldenburg LIK, Haugaard SP, Karlsson T, Kegel-Hübner V, Parwez M, Wiingaard C, Flint A. Renal impairment does not affect pharmacokinetics, safety or tolerability of zenagamtide. Diabetes Obes Metab. 2026;28(10):8946-8954. PMID: 42443140. (Also reports the oral phase 1 weight result.)
5. Mora P, Aroda VR, Asong M, Blüher M, Carlander AF, Kaltoft M, Vilsen LN, Rosenstock J. 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.
6. Mora P, Aroda VR, Asong M, Blüher M, Heftdal LD, Carlander AF, Vilsen LN, Rosenstock J. 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.
7. Kamrul-Hasan ABM, Khalil I, Mahajan K, Dutta D, Banerjee M, Pappachan JM. 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.
8. Moiz A, Filion KB, Samuels AE, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists and co-agonists for weight loss among adults without diabetes: an updated systematic review. Ann Intern Med. 2026. PMID: 42673585.
9. Alhazmi A, le Roux CW. Amylin analogs: the next major class of weight loss therapy: a review of experimental data and early-phase clinical trials. Diabetes Obes Metab. 2026;28(Suppl 5):42-50. PMID: 42452898.
10. Bailey CJ, Flatt PR, Conlon JM. Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Peptides. 2026;196:171480. PMID: 41747885.
11. Son JW, le Roux CW, Blüher M, Nauck MA, Lim S. Novel GLP-1-based medications for type 2 diabetes and obesity. Endocr Rev. 2026;47(2):159-177. PMID: 41054801.
12. World Health Organization. International Nonproprietary Names for Pharmaceutical Substances (INN): Proposed INN List 133. WHO Drug Information. 2025;39(2). Entry “zenagamtide.” cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl133.pdf. Read September 29, 2026.
13. Novo Nordisk. Novo Nordisk successfully completes phase 1b/2a trial with subcutaneous amycretin in people with overweight or obesity. Company announcement No 4/2025, January 24, 2025. Form 6-K: sec.gov/Archives/edgar/data/353278/000117184325000397/f6k_012425.htm. Read September 29, 2026.
14. Novo Nordisk. Novo Nordisk to advance subcutaneous and oral amycretin for weight management into phase 3 clinical development. Company announcement No 17/2025, June 12, 2025. Form 6-K: sec.gov/Archives/edgar/data/353278/000117184325003877/f6k_061225.htm. Read September 29, 2026.
15. Novo Nordisk. Novo Nordisk phase 2 trial with amycretin reports significant weight loss and HbA1c reduction in type 2 diabetes. Company announcement No 38/2025, November 25, 2025. Form 6-K: sec.gov/Archives/edgar/data/353278/000117184325007566/f6k_112525.htm. Read September 29, 2026.
16. Novo Nordisk. Financial report for the period 1 January 2025 to 31 December 2025. Company announcement No 4/2026, February 3, 2026. Form 6-K: sec.gov/Archives/edgar/data/353278/000035327826000006/caq42025.htm. Read September 29, 2026. (“zenagamtide (previously amycretin).”)
17. Novo Nordisk. Financial report for the period 1 January 2026 to 31 March 2026. Company announcement No 30/2026, May 6, 2026. Form 6-K: sec.gov/Archives/edgar/data/353278/000035327826000018/caq12026.htm. Read September 29, 2026. (AMAZE programme initiated.)
18. Novo Nordisk. Financial report for the period 1 January 2026 to 30 June 2026. Company announcement No 48/2026, August 4, 2026. Form 6-K: sec.gov/Archives/edgar/data/353278/000035327826000023/caq22026.htm. Read September 29, 2026. (HF-POLARIS and AMAZE 8 initiated.)
19. ClinicalTrials.gov (API v2). Completed trials, read September 29, 2026: NCT05369390, NCT06049329, NCT06064006, NCT06461039, NCT06478563, NCT06542874, NCT06559527, NCT06820476, NCT07121153.
20. ClinicalTrials.gov (API v2). Phase 3 trials, read September 29, 2026: NCT07339423 (AMAZE 1), NCT07533175 (AMAZE 2), NCT07571005 (AMAZE 3), NCT07571109 (AMAZE 4), NCT07481630 (AMAZE 5), NCT07509307 (AMAZE 6), NCT07668414 (AMAZE 7), NCT07400107 (AMAZE 8), NCT07720271 (AMAZE 9), NCT07822061 (AMAZE 10), NCT07503210 (AMAZE 12), NCT07668401 (AMAZE 13), NCT07797335 (AMBITION 7), NCT07567001 (HF-POLARIS).
21. ClinicalTrials.gov (API v2). Phase 1 trials recruiting or not yet recruiting, read September 29, 2026: NCT07508020, NCT07535307, NCT07587710, NCT07757087, NCT07815067.
22. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org.
23. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (categories 1–3). Updated May 14, 2026. fda.gov/media/94155/download.
24. Code of Federal Regulations. 21 CFR 216.23, Bulk drug substances that can be used to compound drug products in accordance with section 503A. ecfr.gov. Read September 29, 2026.
25. FDA. Drugs@FDA, drug labels and NDC directory via openFDA (api.fda.gov), and NLM DailyMed: searches for amycretin, zenagamtide and NNC0487-0111, September 29, 2026 (no records).
26. NCBI PubMed. Search for amycretin, zenagamtide or NNC0487-0111, September 29, 2026 (26 records).

Related Research

• CagriSemaCagrilintide + Semaglutide (the same pairing as two drugs)
• RetatrutideGIP / GLP-1 / Glucagon Receptor Agonist
• SemaglutideGLP-1 Receptor Agonist (comparator in AMAZE 7 and 8)
• CagrilintideLong-Acting Amylin Analog
• EloralintideLong-Acting Amylin Analog
• PetrelintideLong-Acting Amylin Analog
• MariTideGLP-1 Receptor Agonist + GIP Receptor Antagonist (maridebart cafraglutide)
• PramlintideThe First Approved Amylin Analog