Amycretin: What the Evidence Actually Shows

Amycretin is a real, investigational Novo Nordisk compound in active clinical development for obesity and type 2 diabetes — and a live check run for this article turned up something worth stating in the first paragraph rather than burying: it has been renamed. The most recent published trial data, from two Lancet papers dated July 30, 2026, refers to it throughout as "zenagamtide (formerly amycretin)." This article uses "amycretin" in its title and URL because that's the name people are actually searching, but every claim below reflects the current, renamed compound and its most recently confirmed mechanism.

A real correction the live check surfaced: three receptors, not two

Amycretin has generally been described — including in its own first two published human trials — as a "GLP-1 and amylin receptor agonist." That description is incomplete. The compound's own earliest preclinical characterization paper found something broader: "Amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors in cell-based systems¹." The calcitonin-receptor activity was there from the start, just not emphasized in the human trials' own framing until the most recent Phase 2 publications caught up to it — both 2026 zenagamtide papers now describe it plainly as "a novel unimolecular [peptide] agonist of GLP-1, amylin, and calcitonin receptors⁵⁶." This article states the fuller, three-receptor mechanism because it's what the most current, most complete source actually supports — not because the two-receptor description used in 2025 was fabricated, but because it was an earlier, narrower characterization since superseded by the compound's own sponsor's more recent publications.

Two formulations, tested in genuine parallel — confirmed, not assumed

The dual-formulation development track is real and directly documented. Novo Nordisk ran first-in-human trials for both an oral tablet (NCT05369390) and a subcutaneous injection (NCT06064006) at the same time, publishing both papers in the same July 12, 2025 issue of the Lancet²³. The Phase 2 dose-finding program under the new name repeated that exact structure a year later: once-weekly subcutaneous zenagamtide and once-daily oral zenagamtide, both drawn from the same underlying trial (NCT06542874), both published the same day, July 30, 2026⁵⁶. A separate, earlier Japanese Phase 1 oral trial (compound code NNC0487-0111) is also on record, completed in 2023⁷. This is a real, sustained, deliberately parallel oral-and-injectable program, not a single formulation with an occasional alternate-route side study.

The real topline obesity data — subcutaneous formulation

The subcutaneous Phase 1b/2a trial (125 participants with overweight or obesity, up to 36 weeks) is the strongest published weight-loss evidence for this compound to date, read directly from the trial's own reported findings: at the 60mg dose, mean bodyweight fell 24.3% by week 36, versus 1.1% with placebo (P<0.0001)². At 20mg, the effect was 22.0% versus 1.9% (week 36); at 5mg, 16.2% versus 2.3% (week 28); at the lowest tested dose, 1.25mg, 9.7% versus 2.0% (week 20)². Those are large effect sizes even for this drug class, though the trial's own interpretation is appropriately cautious: it describes these as results that "support further investigation into the weight loss properties of amycretin," not a confirmed, mature efficacy finding — this was a safety-and-tolerability-primary trial, with bodyweight as a secondary endpoint, in a relatively small population with meaningful dropout.

The oral formulation's own data — safety-focused, weight data not yet detailed

The parallel first-in-human oral trial (144 participants across four dose-escalation sub-parts, up to 12 weeks of dosing in its longest arm) was designed primarily to establish safety and pharmacokinetics, not to report a topline weight-loss number — its own published abstract states bodyweight and fasting glucose as "exploratory pharmacodynamic endpoints" without quantifying the actual percentage change in the abstract text itself³. Treatment-emergent adverse events occurred in 62% of participants across all parts, dose-dependent in frequency, predominantly gastrointestinal and mild-to-moderate in severity, with no deaths reported³. This article does not invent a weight-loss figure the trial's own published abstract doesn't state at that level of detail — the oral formulation's real efficacy case, at this stage, rests on the drug reaching the same target and being safe and tolerable at meaningful doses, not yet on a headline percentage.

What the newest (2026) data adds: real Phase 2 results in type 2 diabetes

The most recent published data — under the new name, zenagamtide — moved past the obesity-focused Phase 1/1b-2a program into formal Phase 2 dose-finding for type 2 diabetes, both formulations, both published July 30, 2026. Subcutaneous zenagamtide (six doses, 0.4-40mg, 261 participants, 36 weeks) reduced HbA1c by 0.9 percentage points at the lowest dose up to 1.7 points at the highest, each significantly better than placebo (P=0.0021 to P<0.0001)⁵. Oral zenagamtide (three doses, 6/25/50mg, 186 participants, 36 weeks) reduced HbA1c by 0.9 to 1.4 percentage points versus placebo, all statistically significant⁶. Both trials report a safety and tolerability profile "consistent with that of other GLP-1-based and amylin-based therapies" — real, dose-ranging efficacy data in a diabetes population, published within the last two weeks of this review, confirming the program has real momentum rather than having stalled after its early obesity readouts.

Where it stands right now: Phase 3 obesity trials registered, not yet recruiting

A live ClinicalTrials.gov check found the real next step already on the public record: three named Phase 3 obesity trials under the AMAZE program, all listed NOT_YET_RECRUITING as of this review — "AMAZE 13" (Asia-focused), a head-to-head trial against semaglutide, and "AMAZE 9" (the oral tablet formulation specifically), with estimated start dates between September 2026 and January 2027. That's a real, concrete, dateable next step — not a rumor, and not yet an actual trial with enrolled patients. Zenagamtide/amycretin has no approval anywhere, under either name, as of this review.

What this means if you're considering it

Amycretin — now officially zenagamtide — is real, in active, well-funded Phase 2/3 development at Novo Nordisk, with genuinely substantial early weight-loss data for its subcutaneous formulation and a real, dual-track oral program running in parallel. Its mechanism is broader than commonly described: a triple GLP-1/amylin/calcitonin receptor agonist, not the dual agonist it was initially characterized as. It is not approved, not sold anywhere, and Phase 3 obesity trials are registered but not yet recruiting patients. For how it compares to the other next-generation compounds this site tracks, see our tirzepatide vs. semaglutide evidence review for the current approved standard, and our VK2735 evidence review for a different pharmaceutical company's competing dual-agonist candidate at a similar stage of development.