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

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]

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 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, takes the two-drug route instead, and Lilly and Zealand are testing amylin-only drugs 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. For what happened to another promising oral compound whose trial worked while most participants did not finish it, see danuglipron. For the approved oral small molecule, see orforglipron.