Novo Nordisk to move experimental obesity drug amycretin into Phase 3 trials

Novo Nordisk plans to move amycretin, an experimental obesity drug that acts on two hormone receptors at once, directly into late-stage human testing. The company announced the decision on June 12, 2025, saying both a once-weekly injection and a once-daily pill version will enter Phase 3 development, with the first trial in adults who are overweight or have obesity expected to begin in the first quarter of 2026 ^[3][4].

Amycretin is a single molecule that activates both the GLP-1 receptor — the target of Ozempic, Wegovy and Rybelsus (semaglutide) — and the amylin receptor ^[1]. Its early results were published in The Lancet on June 20, 2025 ^[1].

The injectable data come from a Phase 1b/2a trial at a single center in San Antonio, Texas, that randomly assigned 125 adults aged 18 to 55 with a body mass index of 27.0 to 39.9; 101 received amycretin and 24 received placebo ^[1][2].

Weight loss rose with dose. At the highest dose tested, up to 60 mg once weekly, participants lost an estimated mean 24.3% of body weight after 36 weeks, compared with 1.1% for placebo ^[2]. At 20 mg, the reduction was 22.0% versus a 1.9% gain for placebo at week 36; at 5 mg, 16.2% versus a 2.3% gain at week 28; and at 1.25 mg, 9.7% versus a 2.0% gain at week 20 ^[2]. Novo Nordisk highlighted the top figure as up to 24.3% ^[1], while some coverage of the same trial cites up to 22%, which matches the 20 mg dose rather than the highest one ^[3][4].

The most common side effects were gastrointestinal, mostly mild to moderate, and they became more frequent at higher doses ^[1]. The Lancet abstract notes that a large number of participants withdrew from the study, with a high share of those discontinuations for reasons unrelated to side effects ^[2]. Novo Nordisk said no weight-loss plateau was seen at the end of treatment in either trial ^[1].

The oral version was tested in a separate Phase 1 trial of 144 adults with overweight or obesity. Exploratory results showed a mean weight loss of 13.1% after 12 weeks at 100 mg per day, compared with 1.2% for placebo ^[1]. The most common side effects were nausea, vomiting and decreased appetite, most frequent at higher doses ^[1]. The company said longer studies with more participants are needed to confirm the oral form's effects on weight and metabolic measures ^[1].

These are not head-to-head comparisons. A 14% body weight change at week 36 for Wegovy cited in one report comes from a different Phase 2 study ^[4], so cross-trial numbers cannot show which drug works better. Amycretin has not been approved in the US for weight loss ^[1].

Why it matters for patients

The drugs people can get today are not changing. Ozempic, Wegovy and Rybelsus are all semaglutide, and Mounjaro and Zepbound are tirzepatide. Amycretin is a different molecule and is not available, so it is not something patients can currently be prescribed ^[1].

If it succeeds in Phase 3, amycretin would add a third mechanism for weight management by pairing GLP-1 with amylin, a hormone that also affects appetite. Novo Nordisk is separately testing cagrisema, which combines semaglutide with the amylin drug cagrilintide in a two-chamber pen, while amycretin puts both activities into one molecule ^[3]. Other companies are pursuing amylin-based drugs too, including Eli Lilly, Roche with Zealand Pharma, AbbVie with Gubra, and Metsera ^[3].

An oral version would matter for people who prefer not to inject. But the oral amycretin data so far cover only 12 weeks and 144 people, well short of what regulators require ^[1].

Side effects are the other practical issue. Gastrointestinal symptoms are common across this drug class, and in the injectable trial they increased with dose ^[1][2]. How well people tolerate the higher doses over longer periods has not been reported.

What happens next

Novo Nordisk plans to start Phase 3 testing of injectable and oral amycretin in adults who are overweight or have obesity in the first quarter of 2026 ^[4]. Detailed injectable results are scheduled for a late-breaking poster session on June 22, 2025 at the American Diabetes Association's 85th Scientific Sessions ^[1]. The company has not disclosed the size, duration or endpoints of the Phase 3 program ^[1][4]. One market research firm, GlobalData, forecasts US approval in the fourth quarter of 2030 and European approval in the first quarter of 2031 if the trials succeed ^[4].