Novo Nordisk provided detailed Phase II data for zenagamtide (previously amycretin) in type 2 diabetes at the ADA 2026 Scientific Sessions, supporting the drug's entry into Phase III study. The molecule demonstrated statistically significant A1C reductions and up to 14.6% body weight loss at 36 weeks — with Phase III development set to begin in H2 2026. The data adds to a previous release of topline numbers in November 2025.
Zenagamtide is a unimolecular peptide that simultaneously activates GLP-1 and amylin receptors, a mechanistic combination that distinguishes it from approved GLP-1 receptor agonists and positions it as a potential successor to Novo Nordisk's existing semaglutide franchise in diabetes.
Trial data
The Phase II dose-finding study was a 36-week, randomized, double-blind, placebo-controlled trial enrolling 262 adults with type 2 diabetes inadequately controlled on metformin, with or without an SGLT2 inhibitor (baseline A1C 7.8%; mean body weight 99.2 kg). Six subcutaneous doses ranging from 0.4 mg to 40 mg once weekly were evaluated against matched placebo. The study met its primary endpoint of A1C reduction across all doses. At the highest dose of 40 mg, the estimated mean A1C change from baseline was −1.71 percentage points (estimated treatment difference vs placebo: −1.56%; 95% CI: −2.05, −1.07; p < 0.0001), with up to 89.1% of participants achieving A1C below 7%.
On the key supportive secondary endpoint, mean body weight reduction reached 14.6% with the 40 mg dose versus 2.1% with placebo, and no weight loss plateau was apparent at week 36. Notably, higher-dose participants were exposed to maintenance dosing for only a short period — 8 weeks at 20 mg and 4 weeks at 40 mg — suggesting the efficacy signal may not yet reflect the full treatment effect. Gastrointestinal adverse events were the most common, predominantly mild to moderate in severity, consistent with the profile of other incretin and amylin-based therapies.