Novo's GLP-1/Amylin Dual Agonist Amycretin to Enter Late-Stage Trials for Obesity
Both oral and subcutaneous formulations of the long-acting GLP-1 and amylin receptor agonist move into stage 3 clinical trials following positive feedback from regulators.
Novo Nordisk announced on June 12, 2025, that it will advance both subcutaneous and oral formulations of its investigational dual receptor agonist amycretin into phase 3 clinical development for weight management, following end-of-phase 2 discussions with regulatory authorities. The company plans to initiate the phase 3 program in adults with overweight or obesity in the first quarter of 2026, according to a statement.1
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“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,” Martin Lange Holst, executive vice president for development at Novo Nordisk, said in the statement. “We are excited about the amycretin molecule, and this marks an important step forward.”1
Amycretin is a first-in-class, unimolecular long-acting glucagon-like peptide-1 and amylin receptor agonist being developed for once-daily oral and once-weekly subcutaneous administration. Results from phase 1 and 1b/2a trials have shown robust weight loss and a safety profile consistent with other incretin-based medications. In a randomized, placebo-controlled phase 1b/2a study of subcutaneous amycretin that enrolled 125 adults with overweight or obesity, participants receiving the highest tested dose of 20 mg lost an average of 22% of body weight over 36 weeks compared with a 2% weight gain in the placebo group. Those on intermediate doses of 5 mg for 28 weeks and 1.25 mg for 20 weeks lost 16.2% and 9.7% of body weight, respectively, while placebo groups in these arms gained 2.3% and 1.9%, respectively. Adverse events were predominantly gastrointestinal and mild to moderate in severity.2,3
Earlier data on the oral formulation of amycretin were presented at the September 2024 annual meeting of the European Association for the Study of Diabetes. In that first-in-human trial, participants receiving the highest dose evaluated, 2×50 mg, experienced a mean 13.1% reduction in body weight over 12 weeks, compared to 1.1% in the placebo group (P <.001).4,5 Lower doses of 50 mg once daily led to a 10.4% average reduction. Investigators noted that weight loss had not plateaued by week 12, suggesting the potential for further weight reduction with longer treatment duration. The safety and tolerability of oral amycretin were acceptable across dose levels when titrated gradually, though tolerability declined at higher initial doses without titration.4,5
These oral results marked a notable advancement in the antiobesity drug landscape. At Novo Nordisk’s 2024 capital markets day, company leaders reported that the 13% reduction in baseline weight seen with oral amycretin at 12 weeks exceeded the 6% reduction achieved with semaglutide (marketed by Novo Nordisk as Wegovy) at the same time point. While data from the oral study had not yet undergone peer review or been published at that time, Novo’s Lange Holst told Forbes that the early results justified the transition into mid-stage trials.6
In addition to the amycretin program, Novo is investigating other candidates, including a novel amylin monotherapy and an unspecified tri-agonist compound for weight management and with potential to improve conditions comorbid with obesity. In March 2025, the company announced preliminary findings from the phase 3 REDEFINE 2 trial of CagriSema, its subcutaneous fixed dose combination of semaglutide and long-acting amylin analogue cagrilintide. In that study, participants with overweight or obesity and type 2 diabetes treated with CagriSema saw a mean weight loss of 13.7% vs 3.4% for those treated with placebo. The phase 3 REDEFINE-4 trial, a head-to-head comparison with Eli Lilly's tirzepatide (Zepbound), is ongoing.7
