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AMIRAVOResearch Library

Semaglutide vs amycretin

Semaglutide is an FDA-approved GLP-1 receptor agonist, while amycretin (renamed zenagamtide) is an investigational single molecule that activates GLP-1 and amylin receptors and, per 2026 reports, calcitonin receptors 1,2,3. Both are developed by Novo Nordisk 4,5. A phase 3 trial comparing subcutaneous zenagamtide with semaglutide in obesity (AMAZE 7) began recruiting in 2026, so no head-to-head results were available as of 24 October 2026 6.

Unbranded reference vial illustrating Semaglutide; not an actual product
Semaglutide
FDA-approved
Unbranded reference vial illustrating Amycretin; not an actual product
Amycretin
Investigational

Side by side

FieldSemaglutideAmycretin
ClassGLP-1 receptor agonist 1Unimolecular GLP-1, amylin and calcitonin receptor agonist (investigational) 3
Origin and structureGLP-1 analogue with 94% homology to human GLP-1 and a C18 fatty diacid at lysine 26 for albumin binding 1Single peptide combining GLP-1 and amylin activity, with a C18 diacid-based side chain at lysine 37 of the GLP-1 part 7
Proposed mechanismActivates the GLP-1 receptor; in animals it activated brain regions involved in food intake 1Activated GLP-1, amylin and calcitonin receptors in cell systems and reached brain areas regulating food intake in mice 8
Half-lifeAbout 1 week per the FDA labels 1,9Geometric mean 88.1 hours after a single subcutaneous dose with normal kidney function 7
Highest human trial phaseApproved; phase 3 and outcome trials published 4,10Phase 3 registered (AMAZE 7, recruiting) 6; phase 2 published 3,11
FDA statusApproved as Ozempic (5 December 2017) and Wegovy (4 June 2021), per Drugs@FDA as of 24 October 2026 2Not approved; no Drugs@FDA record under either name as of 24 October 2026 12,13
Published human outcomesSTEP 1: -14.9% vs -2.4% at 68 weeks 4; SELECT: cardiovascular events hazard ratio 0.80 10Phase 1b/2a: -9.7% to -24.3% across escalation parts vs -1.1% to +2.3% with placebo 5; phase 2 type 2 diabetes: HbA1c change -0.9% to -1.7% 3
Safety signalsBoxed warning for thyroid C-cell tumours seen in rodents; gastrointestinal reactions most common 1; more retinopathy complications in SUSTAIN-6 14Mostly mild to moderate gastrointestinal events 3,5; serious adverse events in 8% of the subcutaneous type 2 diabetes trial 3
WADA statusNot named on the 2026 Prohibited List 15; GLP-1 receptor agonist status unchanged for 2027 16Not named on the 2026 Prohibited List; class S0 covers drugs under clinical development with no current approval by any governmental health authority 15
Who funded the evidenceNovo Nordisk 4,10Novo Nordisk 3,5,17

Semaglutide: what the data says

Semaglutide is FDA-approved for type 2 diabetes, cardiovascular and kidney risk reduction in specified groups, chronic weight management and, under accelerated approval, MASH with moderate to advanced fibrosis 1,9.

  • In STEP 1 (1961 adults; human data), body-weight change at 68 weeks was -14.9% vs -2.4% with placebo 4.
  • In SELECT (17,604 adults with cardiovascular disease; human data), the primary cardiovascular outcome occurred in 6.5% vs 8.0% with placebo 10.

Amycretin: what the data says

Amycretin has been studied in oral and subcutaneous forms in trials funded by Novo Nordisk 5,11,17.

  • In a phase 1b/2a study in 125 adults with overweight or obesity (human data), body-weight change ranged from -9.7% to -24.3% across escalation parts vs -1.1% to +2.3% with placebo; a large number of participants withdrew 5.
  • In 36-week phase 2 type 2 diabetes trials (human data), HbA1c fell by 0.9% to 1.7% with subcutaneous and 0.9% to 1.4% with oral amycretin 3,11.
  • In diet-induced obese rats (animal data), 21 days of amycretin reduced body weight by 18% and improved liver steatosis 8.

Key research differences

  • Receptor targets: semaglutide acts on the GLP-1 receptor; amycretin adds amylin (and calcitonin) receptor activity in one molecule 1,3.
  • Regulatory status: semaglutide is FDA-approved; amycretin had no Drugs@FDA record under either name on 24 October 2026 2,12,13.
  • Half-life: about 1 week for semaglutide per its labels vs 88.1 hours after a single amycretin dose 1,7.
  • Evidence depth: semaglutide has completed cardiovascular and kidney outcome trials, whereas amycretin's published human data are phase 1 and phase 2 studies 3,5,10,18.
  • Head-to-head: AMAZE 7, a phase 3 trial of subcutaneous zenagamtide vs semaglutide with an estimated 650 participants, began in September 2026 6.

Where the evidence is limited

No completed head-to-head trial was available as of 24 October 2026; AMAZE 7 was recruiting 6. Amycretin's published trials are small, short and dose-finding, and percentages from escalation parts are not comparable with 68-week phase 3 results for semaglutide 4,5. Both drugs are developed and their trials funded by Novo Nordisk 4,5.

Frequently asked questions

Has amycretin been compared with semaglutide?
A phase 3 head-to-head trial, AMAZE 7, started recruiting in September 2026; no results were available as of 24 October 2026 6.
Does amycretin lead to more body-weight change than semaglutide?
This cannot be determined yet. The published amycretin trials are early-phase and differ in design and duration from semaglutide's phase 3 trials 4,5.
Is amycretin FDA-approved?
No. OpenFDA queries of Drugs@FDA on 24 October 2026 returned no application record for amycretin or zenagamtide 12,13.

References

  1. WEGOVY (semaglutide) injection and tablets: prescribing information, DailyMed set ID ee06186f-2aa3-4990-a760-757579d8f77b (label version dated 18 June 2026) FDA label (via openFDA). 2026
  2. Drugs@FDA application records for NDA 215866 (Mounjaro), NDA 217806 (Zepbound), NDA 209637 (Ozempic), NDA 215256 (Wegovy), NDA 022341 (Victoza) and NDA 206321 (Saxenda): original approval dates (queried 24 October 2026) Drugs@FDA (via openFDA). 2026
  3. 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
  4. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) N Engl J Med. 2021
  5. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study Lancet. 2025
  6. AMAZE 7: Efficacy and Safety of Zenagamtide s.c. Once-weekly Compared to Semaglutide s.c. Once-weekly in Participants With Obesity (NCT07668414), registry record ClinicalTrials.gov. 2026
  7. Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide (full text) Diabetes Obes Metab. 2026
  8. 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
  9. OZEMPIC (semaglutide) injection: prescribing information, DailyMed set ID adec4fd2-6858-4c99-91d4-531f5f2a2d79 (label version dated 1 June 2026) FDA label (via openFDA). 2026
  10. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) N Engl J Med. 2023
  11. 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
  12. Drugs@FDA application data queried through openFDA for amycretin (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  13. Drugs@FDA application data queried through openFDA for zenagamtide (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  14. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) N Engl J Med. 2016
  15. The 2026 Prohibited List - World Anti-Doping Code, as published in the Netherlands Treaty Series (Tractatenblad 2026, 25; Council of Europe Anti-Doping Convention appendix, in force 1 January 2026) Tractatenblad (Official Publications of the Kingdom of the Netherlands). 2026
  16. WADA publishes 2027 Prohibited List (news release, 21 September 2026) World Anti-Doping Agency. 2026
  17. 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
  18. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW) N Engl J Med. 2024

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.