The investigational once-weekly drug lowered A1C and body weight in adults with type 2 diabetes, with Novo Nordisk planning Phase III testing in the second half of 2026.
Novo Nordisk reported Phase II data showing that its investigational once-weekly injectable drug zenagamtide reduced both blood sugar and body weight in adults with type 2 diabetes.
Zenagamtide, also known as amycretin, is a single peptide molecule that activates both GLP-1 and amylin receptors. GLP-1 drugs help regulate blood sugar and appetite, while amylin is involved in fullness and glucose control after meals.
The 36-week, randomized, double-blind, placebo-controlled dose-finding trial enrolled 262 adults whose type 2 diabetes was not adequately controlled on metformin, with or without an SGLT2 inhibitor. To understand which dose might work best, researchers tested six once-weekly under-the-skin doses of zenagamtide, ranging from 0.4 mg to 40 mg, against placebo. A1C, a blood test that estimates average blood sugar over about three months, ranged from 7.0% to 10.0% at baseline.
Zenagamtide met its main goal by significantly lowering blood sugar across every dose tested. At the highest dose, 40 mg, A1C fell by 1.71 percentage points, compared with a 0.14 percentage-point reduction for placebo. A1C is a blood test that estimates a person’s average blood sugar over about three months, with a lower percentage generally reflecting better blood sugar control.
Up to 89.1% of participants taking zenagamtide reached an A1C below 7%, a common treatment target for many adults with type 2 diabetes. Participants on the 40 mg dose also spent up to 91.5% of their time in the target blood sugar range, above the international target of 70%.
Zenagamtide also led to greater weight loss than placebo. Participants taking the 40 mg dose lost an average of 14.6% of their body weight by Week 36, compared with 2.1% for placebo. Novo Nordisk said no apparent weight-loss plateau was seen at Week 36 with the higher doses.
In terms of safety, the most common side effects were gastrointestinal, and most were mild to moderate in severity.
The results were presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA). Based on the findings, Novo Nordisk plans to start a Phase III development program for zenagamtide in adults with type 2 diabetes in the second half of 2026.
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These findings place zenagamtide in running to develop next-gen metabolic drugs. While early treatments focused on a single hormone, other companies are now testing molecules that target two or even three receptors at once.
The competitive field is expanding quickly. Eli Lilly’s retatrutide targets GIP, GLP-1 and glucagon receptors and has reported Phase III data showing weight loss in obesity and A1C reductions in type 2 diabetes. Roche and Zealand Pharma’s petrelintide is a long-acting amylin analog that is planned for Phase III testing in chronic weight management. Viking Therapeutics’ VK2735 targets GLP-1 and GIP receptors and is being developed in both oral and injectable forms.
Boehringer Ingelheim and Zealand Pharma’s survodutide targets GLP-1 and glucagon receptors and has reported Phase III data showing weight loss and reductions in liver fat.
Pfizer is also advancing berobenatide, an investigational GLP-1 that could stand out because it is being studied as a potential once-monthly treatment. The drug is moving into Phase III testing for chronic weight management and obesity-related conditions.
Zenagamtide is also being studied separately for adults with overweight or obesity, and Novo Nordisk is investigating both injectable and oral forms of the drug.
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