Amycretin: The Research Behind Novo Nordisk's Dual-Receptor Agonist

CagriSema is a fixed-dose combination of two independently developed molecules — cagrilintide, an amylin-receptor agonist, and semaglutide, a GLP-1-receptor agonist — co-formulated in one injection. Amycretin takes a different engineering approach: published trial reports describe it directly as a "novel, unimolecular GLP-1 and amylin receptor agonist," meaning one peptide chain is built to act on both receptor families itself, rather than combining two separately developed drugs.^[1][2]

No published head-to-head comparison has tested amycretin directly against CagriSema. CagriSema's own published results, including its phase 3 REDEFINE programme, belong in the cagrilintide research guide rather than repeated here — the two are separate Novo Nordisk development programmes.

An oral, first-in-human, phase 1, double-blind, placebo-controlled trial (NCT05369390) enrolled 144 adults with overweight or obesity at a single San Antonio, TX research unit between May 2022 and January 2024, across single ascending doses (Part A, n=48), multiple ascending doses (Part B, n=36) and a 12-week dose-escalation part (Part C/D, n=60) of oral amycretin up to two 50 mg tablets daily. Its primary endpoint was treatment-emergent adverse events: 364 were reported in 89 of 144 participants (62%), all mild or moderate and increasing with dose; gastrointestinal events were most common (49% of events, in 81% of those with any event). No deaths occurred. Bodyweight and fasting glucose were assessed only as exploratory endpoints in this trial and were not reported as a specific figure in the published results.^[1]

A separate randomised, placebo-controlled phase 1b/2a trial (NCT06064006) tested subcutaneous amycretin, once weekly for up to 36 weeks, in 125 adults with overweight or obesity (101 on amycretin, 24 on placebo) at the same San Antonio site, between September 2023 and April 2024. Here, bodyweight change was a secondary endpoint with a quantified result: at the highest tested dose (60 mg), bodyweight fell by an estimated 24.3% versus 1.1% with placebo at week 36 (p<0.0001); lower maintenance doses of 20 mg, 5 mg and 1.25 mg produced smaller, still statistically significant reductions of 22.0%, 16.2% and 9.7% respectively over shorter treatment periods. The most common adverse events were again gastrointestinal, mostly mild to moderate and resolving by the end of the study; a high proportion of participants who withdrew did so for reasons unrelated to adverse events.^[2]

Two companion phase 2 trials, both registered as NCT06542874 and both published in The Lancet in August 2026, tested amycretin (reported under the name zenagamtide) in adults with type 2 diabetes on stable metformin, with or without an SGLT2 inhibitor. The subcutaneous arm randomised 262 of 915 screened participants (225 to once-weekly zenagamtide across six doses from 0.4 mg to 40 mg, 37 to placebo) across 83 sites in 11 countries, with HbA1c change at week 36 as the primary endpoint. From a baseline HbA1c of 7.8%, results ranged from -0.9% at the lowest dose (treatment difference versus placebo -0.77 percentage points, p=0.0021) to -1.7% at the highest dose, 40 mg (treatment difference -1.56 percentage points, p<0.0001). Serious adverse events occurred in 8% of participants exposed to treatment; none occurred in the placebo group, and no deaths were reported.^[4]

The oral arm of the same trial randomised 186 participants to once-daily zenagamtide (6 mg, 25 mg or 50 mg) or placebo. From a baseline HbA1c around 8%, week-36 reductions ranged from -0.9% at 6 mg (p=0.033) to -1.4% at 50 mg (treatment difference -1.09 percentage points, p<0.0001), with the 25 mg dose reaching -1.3% (p=0.0001). Gastrointestinal adverse events rose with dose, from 26% of participants at 6 mg to 47% at 50 mg, versus 23% on placebo; serious adverse events occurred in 4% of treated participants and none on placebo. No deaths were reported in either the subcutaneous or oral arm of this trial.^[5]

Novo Nordisk's phase 3 programme for amycretin is registered under the name "AMAZE." AMAZE 1 (NCT07339423), testing once-weekly subcutaneous amycretin against placebo in adults with obesity, began recruiting on 24 February 2026 with an estimated 1,150 participants and an estimated primary completion date of 26 June 2029. AMAZE 2 (NCT07533175), covering adults with excess weight and type 2 diabetes, began recruiting on 13 April 2026 with an estimated 630 participants and an estimated primary completion date of 7 August 2028. Status and enrolment figures can move; both are drawn directly from each trial's ClinicalTrials.gov registration as of this article's publication date.^[6][7]

The wider AMAZE programme extends beyond these two flagship trials into additional phase 3 studies in obstructive sleep apnoea, knee osteoarthritis, weight maintenance, and a large cardiovascular-outcomes-style trial in obesity and heart failure (NCT07567001) with an estimated 5,610 participants. None of these later-stage trials has reported results as of September 2026; none should be read as evidence of an approval decision or a confirmed cardiovascular benefit.^[8]

Across all four published human trials — oral phase 1, subcutaneous phase 1b/2a, and the subcutaneous and oral phase 2 diabetes trials — gastrointestinal events (nausea, vomiting, decreased appetite) are consistently the most common adverse events, generally described as mild to moderate and increasing in frequency with dose. No deaths have been reported in any of the four trials. Serious adverse events were reported in a minority of participants in the diabetes trials (8% subcutaneous, 4% oral) and were rare or attributable to a small number of cases in the earlier phase 1 studies.^[1][2][4][5]

Amycretin is one of several long-acting compounds now combining GLP-1 and amylin-pathway biology, alongside Eli Lilly's eloralintide and Novo Nordisk's own CagriSema. This page focuses on amycretin's own published evidence rather than repeating a cross-compound comparison; for how amycretin, eloralintide and CagriSema have been ranked against each other in an indirect network meta-analysis, see the eloralintide vs retatrutide comparison, which covers that evidence in detail.

Amycretin (zenagamtide) has no FDA approval and no EMA authorisation as of September 2026. It remains an investigational compound, tested only inside registered clinical trials, with its phase 3 programme still recruiting and years from completion.^[9]

Peptyds supplies semaglutide as a lyophilised research peptide for in-vitro laboratory work only, with batch documentation described on the quality page. It does not supply amycretin. Nothing on this page is an offer to sell amycretin, and nothing here should be read as instruction for personal or human use of any compound.