Amycretin reduces weight, HbA1c in phase 2 trial

Amycretin reduces weight, HbA1c in phase 2 trial of patients with diabetes

Key takeaways:

• A novel GLP-1 and amylin receptor agonist reduced HbA1c and weight vs. placebo in patients with type 2 diabetes.
• Phase 3 trials of amycretin will begin in 2026.

Amycretin, a novel GLP-1 and amylin receptor agonist, reduced weight and HbA1c in a phase 2 trial of patients with type 2 diabetes, according to topline results announced by Novo Nordisk.

The trial is the first of the drug, which is being developed as a once-weekly subcutaneous agent and a once-daily oral agent, in patients with type 2 diabetes, the company stated in a press release. As Healio previously reported, in trials of patients with obesity, subcutaneous amycretin and oral amycretin conferred significant weight reduction compared with placebo.

The randomized, placebo-controlled phase 2 trial included 448 patients who had uncontrolled type 2 diabetes despite being on metformin, of whom approximately 40% were also taking an SGLT2 inhibitor, according to the release.

The trial was a combined multiple ascending dose study and lasted up to 36 weeks, during which patients were assigned to one of six once-weekly subcutaneous doses from 0.4 mg to 40 mg administered weekly, one of three daily oral doses of 6 mg, 25 mg and 50 mg or placebo, the company stated in the release.

Patients assigned once-weekly subcutaneous amycretin (mean baseline HbA1c, 7.8%) reached dose-dependent reductions in HbA1c of up to 1.8 percentage points at 36 weeks, with 89.1% reaching HbA1c less than 7% and 76.2% reaching HbA1c less than 6.5%, according to the release.

Patients assigned once-daily oral amycretin (mean baseline HbA1c, 8%) reached dose-dependent reductions in HbA1c of up to 1.5 percentage points at 36 weeks, with 77.6% reaching HbA1c less than 7% and 62.6% reaching HbA1c less than 6.5%, according to the release.

The placebo group reached reduction in HbA1c of 0.2 percentage points to 0.4 percentage points, and all comparisons of amycretin to placebo were statistically significant, Novo Nordisk stated in the release.

The subcutaneous amycretin group (mean baseline body weight, 99.2 kg) reached weight loss of up to 14.5% compared with 2.6% for placebo, whereas the oral amycretin group (mean baseline body weight, 101.1 kg) reached weight loss of up to 10.1% compared with 2.5% for placebo, according to the release. Patients assigned to the higher doses of oral or subcutaneous amycretin had no weight-loss plateau at 36 weeks.

The safety profile was consistent with other incretin and amylin-based therapies, and the most common adverse events were gastrointestinal, generally mild to moderate, according to the release.

“We are very encouraged by the phase 2 data with amycretin in people with type 2 diabetes — the first time amycretin has been evaluated in this population. The data further validate the potential best-in-class profile of amycretin,” Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in the release. “Amycretin is built on the complementary biology of GLP-1 and amylin, and we are looking forward to bringing amycretin into an extensive phase 3 development program across multiple indications in 2026.”