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Amycretin

Unimolecular GLP-1 and amylin receptor agonist

Status

In clinical trials

Not approved anywhere and not yet filed; Novo Nordisk started the phase 3 AMAZE program in obesity in 2026 (AMAZE 1 began in February 2026) and plans phase 3 trials in type 2 diabetes.

Evidence

Moderate

Randomized phase 1b/2a and phase 2 trials (Lancet 2025 and 2026) show substantial weight and HbA1c reductions; phase 3 results are not yet available.

In sport

WADAProhibited (WADA)

Amycretin (INN zenagamtide) is an investigational single peptide from Novo Nordisk that activates both GLP-1 and amylin receptors. Tested as a weekly injection and a daily tablet for obesity and type 2 diabetes, it entered phase 3 trials in 2026.

Structure

68 residues

No single sequence to draw

WHO INN list 133 describes zenagamtide as a 68-residue amidated peptide: a GLP-1(7-37) variant (Aib at 2, Glu at 16, Arg at 20 and 28, Lys at 31) joined by a glycine linker to a disulfide-free, calcitonin-based amylin-receptor agonist sequence (residues 36-68), with a C18 diacid via γGlu-2xOEG on Lys31. The amylin-segment sequence is not published in text form, so residues are not listed.

What it is used for

  • Obesity and overweight (studied)
  • Type 2 diabetes (studied)

How it works

Amycretin joins a GLP-1 receptor agonist sequence to an amylin receptor agonist sequence in one molecule, so a single drug engages both appetite pathways that CagriSema targets with two drugs. In cell assays it activated GLP-1, amylin and calcitonin receptors, and in obese rats it cut energy intake by about half. An Aib residue protects the GLP-1 portion from DPP-4, and a C18 fatty diacid on the lysine at the end of the GLP-1 segment binds albumin, supporting weekly injection.

How strong the evidence is

ModerateAt least one good randomised trial, or consistent smaller human trials.

In a phase 1b/2a trial (Lancet 2025; 125 adults with overweight or obesity), weekly injections produced mean weight changes of -22.0% with 20 mg and -24.3% with 60 mg at 36 weeks, versus +1.9% and -1.1% with placebo, although many participants withdrew. A first-in-human trial tested a daily oral tablet. In a 36-week phase 2 trial in 262 adults with type 2 diabetes (Lancet 2026), weekly injections lowered HbA1c by up to 1.7 points and body weight by up to 14.6% at 40 mg, versus 2.1% with placebo.

Risks and side effects

  • Gastrointestinal effects (nausea, vomiting, constipation, diarrhea) are common and dose-dependent, mostly mild to moderate
  • High withdrawal rates in early trials, so tolerability at high doses is uncertain
  • Long-term safety and cardiovascular outcomes are not yet known
  • Not approved: products sold outside clinical trials are unregulated, with unknown identity, purity, dose and sterility

Regulatory status

No regulator has approved this peptide for any use.

Status by country

JurisdictionStatusSource
USUnited StatesNo authorised medicineSource 11
EUEuropean UnionNo authorised medicineSource 12
UKUnited KingdomNo authorised medicineSource 13
AUAustraliaNo authorised medicineSource 14
CACanadaNo authorised medicineSource 15
Whether a medicine containing it is authorised, checked in each regulator’s records on Oct 1, 2026.

Status of every peptide by country

Trials of Amycretin to watch

  1. Phase 3Recruiting

    AMAZE 9(opens the source in a new tab)

    AMAZE 9: A Research Study Investigating How Well Zenagamtide Tablets Help People With Excess Body Weight Lose Weight

    Primary completion expected Jun 27, 2028950 participantsSponsor: Novo Nordisk A/SNCT07720271

  2. Phase 3Recruiting

    AMAZE 3(opens the source in a new tab)

    AMAZE 3: A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Obstructive Sleep Apnoea Not Treated With Positive Airway Pressure Lose Weight and Improve Sleep Apnoea

    Primary completion expected Jul 12, 2028300 participantsSponsor: Novo Nordisk A/SNCT07571005

  3. Phase 3Recruiting

    AMBITION 7(opens the source in a new tab)

    AMBITION 7: A Research Study Investigating How Well Zenagamtide Lowers Blood Sugar and Body Weight Compared to Insulin Glargine in People With Type 2 Diabetes and Increased Risk of Diseases That Affect the Heart and Blood Vessels Treated With 1-3 Other Diabetes Medications

    Primary completion expected Jul 31, 20281,778 participantsSponsor: Novo Nordisk A/SNCT07797335

  4. Phase 3Recruiting

    AMAZE 2(opens the source in a new tab)

    AMAZE 2: A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Type 2 Diabetes Lose Weight

    Primary completion expected Aug 7, 2028630 participantsSponsor: Novo Nordisk A/SNCT07533175

  5. Phase 3Recruiting

    AMAZE 5(opens the source in a new tab)

    A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Knee Osteoarthritis Lose Weight and Reduce Pain

    Primary completion expected Aug 14, 2028400 participantsSponsor: Novo Nordisk A/SNCT07481630

  6. Phase 3Recruiting

    AMAZE 7(opens the source in a new tab)

    A Research Study Investigating How Well the Medicine Zenagamtide Helps People With Excess Body Weight Lose Weight Compared to Semaglutide

    Primary completion expected Oct 10, 2028650 participantsSponsor: Novo Nordisk A/SNCT07668414

  7. Phase 3Not yet recruiting

    AMAZE 8(opens the source in a new tab)

    AMAZE 8: A Research Study Investigating How Well the Medicine NNC0487-0111 Compared to Semaglutide Helps People With Excess Body Weight and Type 2 Diabetes Lose Weight

    Primary completion expected Dec 12, 20281,000 participantsSponsor: Novo Nordisk A/SNCT07400107

  8. Phase 2Completed

    Amycretin in type 2 diabetes(opens the source in a new tab)

    A Research Study Comparing How Well Different Doses of the Medicine NNC0487-0111 Lower Blood Sugar in People With Type 2 Diabetes

    Primary completion Oct 1, 2025448 participantsSponsor: Novo Nordisk A/SNCT06542874

All trials to watch

Timeline

  1. 2028

    1. AMAZE 8
    2. AMAZE 7
    3. AMAZE 5
    4. AMAZE 2
    5. AMBITION 7
    6. AMAZE 3
    7. AMAZE 9

  2. 2026

    1. Trial resultAmycretin, now named zenagamtide, cuts A1C and weight in phase 2 diabetes trial

  3. 2025

    1. Amycretin in type 2 diabetes
    2. Trial resultNovo's amycretin injection shows 22% weight loss at 36 weeks in early-stage trial

Sources

  1. 01International Nonproprietary Names for Pharmaceutical Substances: Proposed INN List 133(opens the source in a new tab) World Health Organization (WHO Drug Information), 2025
  2. 02The effect of amycretin, a unimolecular GLP-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats(opens the source in a new tab) eBioMedicine, 2025
  3. 03Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study(opens the source in a new tab) The Lancet, 2025
  4. 04Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human phase 1 trial(opens the source in a new tab) The Lancet, 2025
  5. 05Efficacy and safety of once-weekly subcutaneous zenagamtide in type 2 diabetes: a phase 2 trial(opens the source in a new tab) The Lancet, 2026
  6. 06Efficacy and safety of once-daily oral zenagamtide in adults with type 2 diabetes: a phase 2 trial(opens the source in a new tab) The Lancet, 2026
  7. 07AMAZE 1: A research study investigating how well NNC0487-0111 helps people with excess body weight lose weight (NCT07339423)(opens the source in a new tab) ClinicalTrials.gov, 2026
  8. 08Novo Nordisk's investigational zenagamtide shows significant A1C reductions with up to 14.6% weight loss in adults with type 2 diabetes (ADA 2026)(opens the source in a new tab) Novo Nordisk via PR Newswire, 2026
  9. 09Novo Nordisk financial report for the first six months of 2026 (Form 6-K)(opens the source in a new tab) U.S. Securities and Exchange Commission (EDGAR), 2026
  10. 10World Anti-Doping Code International Standard: Prohibited List 2026(opens the source in a new tab) World Anti-Doping Agency, 2025
  11. 11Drugs@FDA: FDA-Approved Drugs(opens the source in a new tab) U.S. Food and Drug Administration, 2026
  12. 12Find medicine: centrally authorised medicines(opens the source in a new tab) European Medicines Agency, 2026
  13. 13MHRA Products: active substances beginning with A(opens the source in a new tab) Medicines and Healthcare products Regulatory Agency, 2026
  14. 14Australian Register of Therapeutic Goods (ARTG)(opens the source in a new tab) Therapeutic Goods Administration
  15. 15Drug Product Database online query(opens the source in a new tab) Health Canada
  1. Not approvedAOD-9604Modified growth hormone fragment (research peptide)16 WADA banned
  2. In clinical trialsCagrilintideLong-acting amylin analog (amylin and calcitonin receptor agonist)37 WADA banned
  3. ApprovedDulaglutideGLP-1 receptor agonist (Fc fusion protein)31
  4. ApprovedExenatideGLP-1 receptor agonist39
  5. ApprovedInsulin (human)Peptide hormone (insulin)51 WADA banned

Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.