Novo Nordisk's Zenagamtide Pairs GLP-1 With Amylin in One Molecule, Cutting A1C and Weight in a Phase 2 Trial
The first single-molecule drug to combine GLP-1 and amylin activation showed meaningful glucose and weight effects in type 2 diabetes, an early signal of the field's move into amylin-based therapy.
Novo Nordisk used the American Diabetes Association’s 2026 Scientific Sessions (June 5–8, New Orleans) to present Phase 2 results for zenagamtide, the compound many still know by its development name, amycretin. It is a single peptide that activates two receptors: GLP-1, the target behind semaglutide, and amylin, a satiety hormone co-secreted with insulin that acts on appetite and gastric emptying through a different pathway. Novo’s Martin Holst Lange called it “the first investigational treatment for type 2 diabetes to combine GLP-1 and amylin receptor agonist mechanisms of action in a single molecule.”
The 36-week, randomized, double-blind, placebo-controlled dose-finding study enrolled 262 adults with type 2 diabetes inadequately controlled (A1C 7.0–10.0%) on metformin, with or without an SGLT2 inhibitor. Baseline A1C averaged 7.8% and weight 99.2 kg (about 219 lbs). Six once-weekly subcutaneous doses were tested, from 0.4 mg to 40 mg.
At 40 mg, A1C fell by 1.71 percentage points, versus 0.14 on placebo; 89.1% of that group reached an A1C below 7%, and 76.2% got to 6.5% or lower. Body weight dropped by 14.6% at the top dose, against 2.1% on placebo. The trial met its primary endpoint, A1C reduction, across all doses, and its key secondary endpoint of weight loss at doses of 1.5 mg and above. Gastrointestinal side effects, mostly mild to moderate, tracked what is expected of incretin- and amylin-based drugs.
Two caveats keep the numbers in perspective. First, these are Phase 2, dose-finding data in a comparatively small cohort, presented at a conference rather than published in a peer-reviewed journal. Second, the weight results come from people with type 2 diabetes, who typically lose less than people without it, so the 14.6% figure is not directly comparable to the obesity-trial headlines that dominate this beat.
Still, the readout matters for what it signals. Amylin has become the field’s most-watched second target after GLP-1, and amycretin is being developed in both oral and subcutaneous forms; this study covers the injectable. Novo said it plans to begin a Phase 3 program in type 2 diabetes in the second half of 2026. The company is advancing amycretin alongside CagriSema, its separate cagrilintide-plus-semaglutide combination, meaning it is testing both ways of marrying GLP-1 to amylin, one molecule and two. That parallel bet is a useful tell: after a decade defined by GLP-1, much of the industry’s next chapter is being written around amylin.