Novo Nordisk plans phase 3 trials of amycretin in type 2 diabetes for 2026

Novo Nordisk will start phase 3 trials of amycretin, an experimental drug that targets the GLP-1 and amylin receptors, in type 2 diabetes in 2026, the company said after releasing phase 2 results ^[1]. Novo had previously described amycretin mainly as an obesity prospect ^[1].

The phase 2 study enrolled 448 people with type 2 diabetes that was not adequately controlled on metformin. About 40% of them were taking an SGLT2 inhibitor before joining the trial ^[1]. Participants received a weekly subcutaneous injection or a once-daily oral version of amycretin, or a placebo ^[1].

At Week 36, the subcutaneous injection lowered HbA1c, a measure of average blood sugar over roughly three months, by up to 1.8 percentage points. HbA1c fell 0.2 points in the placebo group. Mean HbA1c was 7.8% at the start of the study. By Week 36, 89.1% of patients on the subcutaneous drug had HbA1c below 7%, and 76.2% were at 6.5% or lower ^[1].

The once-daily oral form lowered HbA1c by up to 1.5 points, compared with 0.4 points for placebo. Baseline mean HbA1c was 8%. HbA1c fell below 7% in 77.6% of patients and to 6.5% or lower in 62.6% ^[1].

Weight also dropped. People on the subcutaneous form lost up to 14.5% of body weight by Week 36, from a mean starting weight of 99.2 kg. Placebo patients lost 2.6%. On the oral form, weight loss reached 10.1% from a mean starting weight of 101.1 kg, compared with 2.5% on placebo ^[1].

The company said weight loss had not plateaued at Week 36 on the higher subcutaneous and oral doses. Patients on the highest subcutaneous dose had been on their final maintenance dose for only four weeks, and Novo said that suggests longer trials could show more weight loss, as has happened in studies of other GLP-1 drugs ^[1].

Side effects were mostly mild to moderate gastrointestinal events. Novo said the tolerability data support further development of amycretin in type 2 diabetes ^[1].

Amycretin is a single molecule that hits the same two receptors as CagriSema, Novo's combination of a long-acting amylin analog and a GLP-1 receptor agonist ^[1]. Novo's chief scientific officer, Martin Holst Lange, said in September that the company's base case is that amycretin will match CagriSema on safety, tolerability and efficacy, and that one molecule would be "a very valuable offering for us" because it can go into a single-chamber device and requires making one active ingredient instead of two ^[1].

For context, Novo reported a 2.2-point mean HbA1c change and 15.6% weight loss at 32 weeks in a small phase 2 trial of CagriSema. In a phase 3 CagriSema trial, body weight fell 13.7% by Week 68, and 73.5% of patients had an HbA1c of 6.5% or less ^[1]. Those were separate studies with different designs, so the numbers are not a direct head-to-head comparison.

Novo shares rose more than 4%, approaching 300 Danish kroner ($46), after the data were released, following a drop the previous day on Alzheimer's disease trial failures ^[1].

Why it matters for patients

Amycretin is not an approved medicine, and neither the company nor regulators have said when it might reach the market ^[1]. Phase 3 trials alone typically take years, so this is a step in testing rather than a treatment people can ask about now.

If it succeeds, it would join a market that already includes injectable drugs such as Ozempic and Wegovy (semaglutide), Mounjaro and Zepbound (tirzepatide), and oral semaglutide, sold as Rybelsus. Amycretin is a different molecule, tested here at two different doses in two different formats, so its results do not apply to any approved product ^[1].

The study tested people whose blood sugar was not controlled on metformin, a common situation in type 2 diabetes. Results in other groups of patients, such as those taking other drug combinations or using insulin, have not been reported ^[1].

The data also do not show how amycretin compares directly with approved GLP-1 medicines, because no head-to-head study has been reported ^[1].

What happens next

Novo has committed to starting phase 3 development of amycretin in type 2 diabetes during 2026 ^[1]. The number of phase 3 trials, where they will run, how many patients they will enroll and when results are expected have not been disclosed ^[1].

It is also not yet known whether the weight loss seen at Week 36 would continue with longer treatment in this patient group, since Novo has only reported that weight loss had not plateaued at that point ^[1].