Novo Nordisk expands the amycretin program into type 2 diabetes

Novo Nordisk has decided to move its experimental drug amycretin, now renamed zenagamtide, into Phase 3 testing for type 2 diabetes starting next year, after Phase 2 data showed strong blood sugar and weight results ^[1]. The drug combines actions on GLP-1 and amylin receptors in a single molecule, and Novo had previously seen it mainly as a candidate for obesity treatment ^[1].

In September, Novo's chief scientific officer said studying the drug in diabetes was "prudent" but that obesity was the company's main focus ^[1]. That changed after Novo saw results from a Phase 2 trial of 448 people with type 2 diabetes that was not well controlled by metformin alone; about 40% were also taking an SGLT2 inhibitor ^[1].

By week 36, people receiving a weekly injected dose of the drug had blood sugar (HbA1c) drop by up to 1.8 percentage points, compared to a 0.2 point drop on placebo, from a starting average of 7.8% ^[1]. Nearly 89% of injected-dose patients got their HbA1c below 7%, and more than 76% got it to 6.5% or lower ^[1]. A once-daily pill version lowered HbA1c by up to 1.5 points, versus 0.4 points on placebo, from a starting average of 8% ^[1].

Weight loss was also measured. Patients on the injected form lost up to 14.5% of body weight by week 36, compared with 2.6% on placebo, from an average starting weight of about 99 kg (218 pounds) ^[1]. Patients on the pill lost up to 10.1%, compared with 2.5% on placebo, from an average starting weight of about 101 kg (223 pounds) ^[1]. Novo noted that people on the highest injected dose had only been at their final dose for four weeks, and weight loss had not leveled off yet in the higher-dose groups — meaning people might lose more weight over a longer trial, as has happened with other GLP-1 drugs ^[1]. Side effects were mostly mild to moderate stomach and digestive issues, similar to other drugs in this class ^[1].

Novo already has late-stage data on CagriSema, a combination of two separate drugs — a long-acting amylin analog and a GLP-1 drug — that work on the same two targets as zenagamtide, which is a single molecule ^[1]. In a CagriSema trial, patients lost 13.7% of body weight at 68 weeks, and 73.5% reached an HbA1c of 6.5% or lower ^[1]. Novo's scientific chief said the company's working assumption is that zenagamtide will perform similarly to CagriSema, but as one molecule it could be easier and cheaper to manufacture and could be delivered from a single-chamber injection device ^[1]. Novo's stock rose more than 4% after the data were released, a day after shares had fallen 8% on news of unrelated Alzheimer's disease trial failures involving semaglutide ^[1].

Why it matters for patients

For people with type 2 diabetes, this news signals that a new class of drug — one that acts on two hormone systems at once, GLP-1 and amylin — could eventually become available in a single injection or pill, rather than requiring two separate drugs like CagriSema ^[1]. The blood sugar and weight results reported so far are similar to those seen with other leading GLP-1 and dual-hormone drugs, according to the source ^[1]. However, this is Phase 2 data. It is not yet known how the drug will perform in the larger, longer Phase 3 trials that are needed before the FDA would consider approving it, and it is not yet approved for any use in the United States.

What happens next

Novo Nordisk has committed to starting Phase 3 trials of zenagamtide in type 2 diabetes during 2026 ^[1]. No specific completion date, trial size, or FDA filing timeline for the diabetes program was given in the source. Novo continues to develop the same drug for obesity as well, though details of that program's next steps were not included in this report ^[1].