Novo Nordisk zenagamtide (amycretin) delivers large HbA1c and weight reductions in phase 2 T2D trial

Study design

The phase 2 trial was a 36‑week, randomized, double‑blind, placebo‑controlled, dose‑finding study of once‑weekly subcutaneous zenagamtide (0.4–40 mg) versus placebo in 262 adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor. Baseline characteristics: mean age 57.1 years, 66% male, mean HbA1c 7.8%, mean body weight 99.2 kg (≈218.7 lbs), and 40% on an SGLT2 inhibitor. The design used fixed‑dose escalation; intolerance led to permanent discontinuation.

Glycaemic efficacy

The study met its primary endpoint of dose‑dependent change in HbA1c at week 36. From a baseline of 7.8%, the largest mean change was −1.71% with 40 mg (ETD vs placebo −1.56%; 95% CI −2.05, −1.07; p<0.0001). Up to 89.1% of participants achieved HbA1c <7% and up to 76.2% achieved ≤6.5%. Time in range (70–180 mg/dL) exceeded the recommended target (>70%) across doses, reaching up to 91.4% with 40 mg. Analyses were based on the on‑treatment without rescue medication observation period and dose–response modelling estimated HbA1c reductions up to −1.8% (ETD −1.58; p<0.0001).

Weight and secondary outcomes

Zenagamtide produced dose‑dependent weight loss, with mean reductions up to 14.6% at 40 mg versus 2.1% with placebo at week 36; baseline weight ≈219 lbs. No clear weight‑loss plateau was observed at higher doses by week 36. Key supportive secondary endpoints included time in range, systolic blood pressure, hs‑CRP and lipids.

Safety and next steps

The most common adverse events were gastrointestinal and mostly mild to moderate; the safety profile was consistent with other incretin and amylin‑based therapies. Based on these phase 2 results, Novo Nordisk plans to initiate a phase 3 development program for adults with type 2 diabetes in H2 2026.