Novo Nordisk's Zenagamtide Delivers Strong Phase II HbA1c and Weight Reductions in Type 2 Diabetes

Novo Nordisk has reported positive Phase II results for zenagamtide, an investigational once-weekly subcutaneous therapy that combines GLP-1 and amylin receptor agonist activity in a single molecule. The data were presented at the American Diabetes Association 2026 Scientific Sessions and show robust improvements in glycaemic control and body weight versus placebo.

Study Design and Participants

The randomised, double-blind, placebo-controlled, dose-finding trial used a fixed-dose-escalation design to evaluate six doses of zenagamtide (0.4 mg to 40 mg) in 262 adults with type 2 diabetes whose glycaemic control remained inadequate on metformin, with or without an SGLT2 inhibitor. The treatment period reported here was 36 weeks.

Key Efficacy Results

The primary endpoint—change in haemoglobin A1c (HbA1c) at 36 weeks—was met at all dose levels. At the highest dose (40 mg), the estimated mean HbA1c reduction was −1.71% versus −0.14% for placebo. Glycaemic control improved across multiple measures: up to 89.1% of participants on zenagamtide achieved HbA1c <7.0%, and up to 76.2% reached HbA1c ≤6.5%.

Continuous glucose-monitoring metrics were also strong: time in range (70 mg/dL–180 mg/dL) exceeded 70% across doses and reached as high as 91.4% at 40 mg.

Weight Loss

For the key secondary endpoint of body weight, mean reductions reached up to 14.6% in the 40 mg group (from a baseline mean of 99.2 kg), compared with a 2.1% reduction in the placebo group. Investigators reported no evidence of a weight-loss plateau at the highest doses tested.

Safety

Adverse events were predominantly gastrointestinal and mostly mild to moderate in severity. Overall safety observations were consistent with therapies that act on GLP-1 and related pathways.

Martin Holst Lange, Executive Vice President and Chief Scientific Officer of R&D at Novo Nordisk, said: "Zenagamtide is the first investigational medicine to combine GLP-1 and amylin receptor agonist activity in a single molecule. These Phase II data add to evidence that the drug can meaningfully improve glucose control and reduce body weight, and position us to advance new treatment options for people with type 2 diabetes and obesity."

Next Steps

Based on these Phase II data, Novo Nordisk plans to advance zenagamtide into Phase III trials for adults with type 2 diabetes in the second half of 2026. Earlier in 2026, the company also reported positive Phase III results for another candidate, CagriSema, versus semaglutide (Ozempic) on both HbA1c and weight.

Overall, zenagamtide's dual mechanism and the magnitude of glycaemic and weight effects observed make it a notable candidate in the evolving T2D and obesity treatment landscape. Phase III results will be important to confirm durability, safety across broader populations, and comparative benefits versus existing therapies.