# Amycretin: A 24% Weight Figure, and the Trial It Came From

By Ruth Calder, Enforcement Editor (https://glpwatchdog.org/authors/ruth-calder) | Published: 2026-08-21 | Updated: 2026-10-27

Canonical page: https://glpwatchdog.org/research/amycretin-what-the-phase-1b-showed

> Once-weekly amycretin produced an estimated 24.3% bodyweight reduction at 36 weeks against 1.1% on placebo. It came from a single-site phase 1b/2a study of 125 people whose primary endpoint was counting adverse events.

## Key points

- Phase 1b/2a, single site, 125 randomized: 101 on amycretin, 24 on placebo.
- Weight change by dose: -9.7% at 1.25 mg, -16.2% at 5 mg, -22.0% at 20 mg, -24.3% at 60 mg. The gradient is orderly across study parts of different durations.
- The primary endpoint was the number of treatment-emergent adverse events; bodyweight was secondary.
- Amycretin, now named zenagamtide, activates both the GLP-1 and amylin receptors. Funded by Novo Nordisk; in phase 3, not approved anywhere.

Amycretin is a single drug built to hit the GLP-1 target and the amylin target at once, instead of pairing two compounds. In its first substantial trial, once-weekly subcutaneous amycretin at 60 mg produced an estimated mean bodyweight change of **−24.3%** at week 36, against −1.1% on placebo.[1] That is a larger figure than anything currently approved. It is also a phase 1b/2a study at one clinical site, with 101 people on the drug, whose primary endpoint was counting adverse events rather than measuring weight.

## What the trial was

It was a randomized, placebo-controlled phase 1b/2a study at a single research center in San Antonio, Texas, in people aged 18 to 55 with a BMI between 27.0 and 39.9. The study ran in five parts (a single ascending dose, a dose-escalation arm and three dose-response arms), with treatment durations between 20 and 36 weeks depending on the part. In all, 125 participants were randomized: 101 to amycretin, 24 to placebo.[1]

*Estimated mean bodyweight change from baseline, by trial part. Parts ran for different durations, so the rows are not a like-for-like ladder.[1]*

| Part | Maintenance dose | Amycretin | Placebo | Timepoint |
| --- | --- | --- | --- | --- |
| B | 60 mg | **−24.3%** | −1.1% | week 36 |
| C | 20 mg | −22.0% | +1.9% | week 36 |
| D | 5 mg | −16.2% | +2.3% | week 28 |
| E | 1.25 mg | −9.7% | +2.0% | week 20 |

The gradient is the most persuasive thing in the table. Each step up in dose brought more weight loss, in order, with no reversal. That is what a real pharmacological effect looks like, and it is harder to produce by accident than a single impressive number. Placebo participants gained weight in three of the four parts.

> **The primary endpoint was the number of treatment-emergent adverse events.** Bodyweight was a secondary endpoint. A trial built to establish safety and pharmacokinetics is not designed to measure efficacy precisely, so its weight figures are encouraging but not established. The study was funded by Novo Nordisk.

## The withdrawals, and what they do and do not mean

The paper records that a large number of participants withdrew, with a high proportion of those discontinuations occurring for reasons *unrelated* to treatment-emergent adverse events.[1] That is different from a trial where people leave because the drug is intolerable. Even so, the withdrawals shrink the group any endpoint is calculated from, in a study that was not large to begin with.

On tolerability itself, gastrointestinal effects led the adverse-event list; most were mild to moderate and had resolved by the end of the study. The authors describe the rates as similar to those seen in early-phase studies of GLP-1 and amylin agonists generally.[1]

## Since this trial: a new name, and phase 3

Novo has renamed the drug. Amycretin is now **zenagamtide**, and the 2026 papers describe it as acting on GLP-1, amylin and calcitonin receptors.[2] Two phase 2 dose-finding trials in type 2 diabetes were published in The Lancet in July 2026, one testing a weekly injection and one a daily pill. Both ran 36 weeks and both measured HbA1c, not weight, as the primary endpoint.

- **Weekly injection:** 225 people on six doses from 0.4 to 40 mg, 37 on placebo. HbA1c fell by 0.9 points at the lowest dose and 1.7 at the highest.[2]
- **Daily pill:** 156 people on 6, 25 or 50 mg, 30 on placebo. HbA1c fell by 0.9, 1.3 and 1.4 points.[3]

Neither abstract reports a weight result, so we give none. Novo has since started a phase 3 program called AMAZE. It includes a two-year head-to-head with semaglutide in type 2 diabetes, due to read out in the first half of 2029, and a heart-failure outcomes trial, HF-POLARIS, of about 5,600 people, due in the second half of 2029.[4] Until then, the −24.3% above is still the largest weight figure, and it still comes from the smallest trial.

## Why adding amylin is the interesting part

Amylin is released alongside insulin; it slows how fast the stomach empties and signals fullness through a different pathway from GLP-1. Novo’s other amylin drug, [cagrilintide](https://glpwatchdog.org/research/cagrilintide-what-the-evidence-shows), takes the two-drug route instead, and Lilly and Zealand are testing [amylin-only drugs](https://glpwatchdog.org/research/amylin-analogs-petrelintide-eloralintide) with no GLP-1 action at all. Reaching both targets from one compound is an attempt to add effect without simply pushing a GLP-1 dose higher. Higher GLP-1 doses are what run into the tolerability ceiling visible in every trial of this class.

Whether that theory survives phase 3 is now being tested, and the first answers are not due until 2029. For another two-mechanism drug already in phase 3, see [MariTide](https://glpwatchdog.org/research/maritide-maridebart-cafraglutide-evidence). For what happened to another promising oral compound whose trial worked while most participants did not finish it, see [danuglipron](https://glpwatchdog.org/research/danuglipron-the-pill-most-people-stopped). For the approved oral small molecule, see [orforglipron](https://glpwatchdog.org/research/foundayo-orforglipron-oral-glp1).

## Frequently asked questions

### How much weight did amycretin produce?

In a phase 1b/2a study, estimated mean bodyweight change at the 60 mg dose was −24.3% at week 36 against −1.1% on placebo. Lower doses produced −22.0% at 20 mg, −16.2% at 5 mg and −9.7% at 1.25 mg, across parts of different durations.

### Is that better than existing drugs?

The figure is larger than anything currently approved, but it comes from an early-phase, single-site trial with 101 people on the drug and weight as a secondary endpoint. Early-phase results routinely shrink in larger studies, and no head-to-head comparison exists.

### What is amycretin?

It is one compound engineered to reach two targets at once, the GLP-1 target and the amylin target. Novo now calls it zenagamtide. Amylin is co-secreted with insulin, slows gastric emptying and signals fullness by a route GLP-1 does not use, so pairing the two actions aims to add effect without pushing GLP-1 dosing higher.

### Is it available?

No. It is investigational and not approved anywhere. Under its new name, zenagamtide, it has completed phase 2 trials in type 2 diabetes and entered phase 3, with the first phase 3 readouts expected in 2029. All of the trials are funded by Novo Nordisk.

### Were there side effects?

The most common were gastrointestinal, mostly mild to moderate, and the majority resolved by the end of the study. A large number of participants withdrew, though the paper notes a high proportion of those withdrawals were for reasons unrelated to adverse events.

## References

1. Dahl K, Toubro S, Dey S, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. The Lancet. 2025. PMID: 40550231. https://pubmed.ncbi.nlm.nih.gov/40550231/
2. Mora P, Aroda VR, Asong M, et al. 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. The Lancet. 2026. PMID: 42532080. https://pubmed.ncbi.nlm.nih.gov/42532080/
3. Mora P, Aroda VR, Asong M, et al. 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. The Lancet. 2026. PMID: 42532079. https://pubmed.ncbi.nlm.nih.gov/42532079/
4. Novo Nordisk A/S Financial report for the period 1 January 2026 to 30 June 2026 (Form 6-K). U.S. Securities and Exchange Commission, August 2026. 2026. https://www.sec.gov/Archives/edgar/data/0000353278/000035327826000023/caq22026.htm

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Cite as: GLP Watchdog, Ruth Calder, "Amycretin: A 24% Weight Figure, and the Trial It Came From", published 2026-08-21, updated 2026-10-27. https://glpwatchdog.org/research/amycretin-what-the-phase-1b-showed

Canonical HTML page: https://glpwatchdog.org/research/amycretin-what-the-phase-1b-showed

Medical disclaimer: Nothing here is medical advice. We report on this subject; we do not treat anyone. Whether to begin a medication, supplement, or treatment, whether to adjust it, and whether to stop are questions for a clinician licensed to answer them, who knows your history.