Novo Nordisk's investigational drug, zenagamtide, has demonstrated an average weight loss of up to 14.6% in individuals with type 2 diabetes. Data from a positive Phase 2 trial, presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans, LA, indicates that zenagamtide is the first drug of its kind to combine two distinct biological mechanisms that regulate metabolism into a single molecule: a GLP-1 receptor agonist and an amylin receptor agonist. While the primary focus of the study was on the drug's effect on blood sugar levels, the results showed that participants receiving zenagamtide once a week experienced an average body weight reduction of 14.6% with the 40 mg dose, compared to just 2.1% with a placebo, which is a dummy treatment with no active medication.
Impact on blood sugar levels
Over the 36-week trial, zenagamtide dramatically reduced HbA1C levels.
The 36-week study tested different doses of the drug against a placebo. Participants started with a baseline HbA1C of 7.8%. Patients taking zenagamtide saw a significant drop in their HbA1C levels. Higher doses, 40 mg, lowered HbA1C by up to 1.71 % compared to just a 0.14 drop in the placebo group. Up to 91.4% of patients across the trial doses hit target glycemic efficacy metrics.
Weight loss effect
Even though the main focus was blood sugar, patients taking the drug lost a substantial amount of weight. From a starting average body weight of roughly 99 kgs (219 lbs), those taking the highest 40 mg dose saw an average body weight reduction of up to 14.6%. In comparison, patients taking the placebo only lost about 2.1% of their weight.
Weight loss without plateau
The scientists noted that the weight loss had not plateaued by week 36, meaning patients would likely continue to lose more weight if they stayed on the higher doses longer.
Furthermore, because of the way the trial was designed, the patients on the highest doses were only taking that final maximum dose for a very short period, which was just 4 weeks for the 40 mg dose. Despite this short exposure, the results were highly effective.
Also read: Ozempic And Wegovy Weight Loss Eventually Plateaus, Study Explains Why
About zenagamtide
Zenagamtide, formerly known as Amycretin, is an experimental, dual-action metabolic medication under development by Novo Nordisk. Unlike older weight loss medications like semaglutide (Wegovy/Ozempic), which target only one hormone receptor, GLP-1, zenagamtide is a unimolecular peptide agonist that targets two distinct metabolic pathways simultaneously:
- GLP-1 Receptor Agonist: Mimics the GLP-1 hormone to stimulate insulin secretion, lower blood sugar, and target brain regions to reduce hunger.
- Amylin Receptor Agonist: Mimics amylin, a hormone co-secreted with insulin that suppresses appetite, slows down food transit, and enhances feelings of fullness.
By combining these two mechanisms into a single molecule, it maximises appetite suppression and glucose regulation.
Martin Holst Lange, chief scientific officer and executive vice president, Research and Development at Novo Nordisk, explained that these results prove the drug has strong potential to meaningfully improve blood glucose control for type 2 diabetes patients while simultaneously helping people manage obesity.
"These results underscore our scientific leadership and position us to continue advancing innovative treatment options that could expand the therapeutic landscape and provide patients and healthcare professionals with greater choice in managing type 2 diabetes and obesity," said Martin Holst Lange.
After these positive results, Novo Nordisk has already moved forward with a larger Phase 3 study, called the AMAZE program, to further evaluate the drug.
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