Novo takes amycretin into late-stage trials in both pill and injection form

Novo Nordisk said it will advance both the injectable and pill versions of amycretin, an experimental drug that acts on GLP-1 and amylin receptors in a single molecule, into phase 3 testing for weight management. The company announced the decision on June 12, 2025, after end-of-phase-2 discussions with regulators, and said it planned to start the phase 3 program in adults with overweight or obesity in the first quarter of 2026 ^[1]. Industry trackers now list amycretin among the drugs in phase 3 development ^[2].

"We are very pleased that the feedback from regulatory authorities has allowed us to take subcutaneous and oral amycretin in weight management to phase 3," said Martin Lange Holst, Novo's executive vice president for development ^[1].

What the early data show

Amycretin is described as a first-in-class, long-acting GLP-1 and amylin receptor agonist, designed for once-daily oral or once-weekly injected use ^[1]. Amylin is a different hormone pathway than GLP-1; combining both in one molecule is the design bet.

In a randomized, placebo-controlled phase 1b/2a study of the injection in 125 adults with overweight or obesity, people on the highest tested dose — 20 mg — lost an average of 22% of body weight over 36 weeks, while the placebo group gained 2% ^[1]. Lower doses produced less weight loss over shorter periods: 16.2% with 5 mg over 28 weeks and 9.7% with 1.25 mg over 20 weeks, compared with placebo gains of 2.3% and 1.9% ^[1]. Side effects were mostly gastrointestinal and mild to moderate ^[1].

The pill version has less data behind it. In a first-in-human trial presented at the European Association for the Study of Diabetes meeting in September 2024, the highest dose tested — 2 x 50 mg — produced a mean 13.1% weight reduction over 12 weeks versus 1.1% with placebo (P<.001), while 50 mg once daily produced 10.4% ^[1]. Investigators said weight loss had not leveled off by week 12, which leaves open the possibility of more loss over longer treatment ^[1]. Tolerability was acceptable when doses were raised gradually but worsened when higher doses were started without titration ^[1].

At Novo's 2024 capital markets day, company leaders said the roughly 13% figure at 12 weeks with the oral drug exceeded the 6% seen with semaglutide (sold as Wegovy) at the same time point — though that comparison came from separate studies, and the oral data had not been peer-reviewed or published at the time ^[1].

Why it matters for patients

These are early- and mid-stage results in small groups, not the kind of large, long-term evidence regulators need before approval. Phase 3 trials are where efficacy numbers often shift. Novo's CagriSema, a weekly semaglutide-plus-cagrilintide combination, delivered about 22.7% weight loss in phase 3 — short of the roughly 25% the company had hoped for ^[2].

Cross-trial comparisons are also unreliable because durations differ. For reference, one pipeline tracker lists tirzepatide at about 21% over 72 weeks, semaglutide at about 15% over 68 weeks, orforglipron (approved as Foundayo in April 2026) at about 15%, Amgen's MariTide at about 20% over 52 weeks, and Lilly's retatrutide at 28.3% over 80 weeks in TRIUMPH-1 ^[2]. Amycretin's 22% came over 36 weeks in a study of 125 people ^[1].

The practical point for patients is that the pipeline is widening in two directions at once: more pills, and more drugs that pair GLP-1 with amylin. Whether amycretin ends up more effective or better tolerated than what is already on pharmacy shelves is not yet known from these sources.

What happens next

Novo guided to a first-quarter 2026 phase 3 start for adults with overweight or obesity ^[1]. The specific trial names, enrollment targets, treatment durations and expected readout dates are not stated in the available sources, and no filing timeline has been given.

Separately, Novo's CagriSema faces an FDA decision in the second half of 2026 ^[2], and its phase 3 REDEFINE-4 head-to-head trial against tirzepatide (Zepbound) is ongoing ^[1]. In REDEFINE 2, CagriSema produced a mean 13.7% weight loss versus 3.4% with placebo in people with overweight or obesity and type 2 diabetes ^[1].