Novo Nordisk announced positive results from a sub-analysis of the phase 3 REDEFINE 1 trial, presented at the European Association for the Study of Diabetes (EASD) congress 2025 in Vienna, Austria. The trial evaluated the efficacy and safety of once-weekly cagrilintide 2.4 mg as monotherapy, combined with lifestyle intervention, in adults with obesity or overweight and a weight-related comorbidity, without diabetes.

Cagrilintide, a long-acting amylin analogue that mimics the naturally occurring hormone amylin, represents a novel approach to obesity management. Unlike currently approved GLP-1-based therapies, cagrilintide works through a different biological pathway. These findings mark the first phase 3 clinical trial data for an investigational long-acting amylin analogue monotherapy in obesity treatment.

In REDEFINE 1, participants receiving cagrilintide achieved an average weight reduction of 11.8 percent of body weight, compared to 2.3 percent with placebo after 68 weeks, when adherence was maintained. On average, participants treated with cagrilintide lost 12.5 kg, compared to 2.5 kg with placebo. In addition, 31.6 percent of participants treated with cagrilintide achieved at least 15 percent weight loss, compared with 4.7 percent in the placebo group. When evaluated regardless of adherence, average weight loss remained significant at 11.5 percent for cagrilintide versus 3.0 percent for placebo, with 31.0 percent of participants achieving weight loss of 15 percent or more compared to 5.2 percent with placebo.

Cagrilintide was generally well tolerated. The most common side effects were gastrointestinal, including nausea, vomiting, diarrhoea and constipation, which were typically transient and mild to moderate in severity. Permanent discontinuation due to nausea occurred in 1.0 percent of participants receiving cagrilintide compared with 0.1 percent of those on placebo.

“These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, improve health outcomes and manage their obesity, with a favourable tolerability profile,” said Timothy Garvey, MD, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham. “As with other chronic diseases, a range of treatment options is needed to meet the individual needs of people with obesity, including variation in their response to treatment.”

Based on these results, Novo Nordisk will advance cagrilintide into the dedicated RENEW phase 3 clinical programme, set to begin in the fourth quarter of 2025.

“Our current and future therapies are designed to help people with obesity achieve meaningful weight loss and broader health benefits,” said Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk. “With obesity affecting millions worldwide, scientific innovation and diverse therapeutic options are critical. In clinical trials, cagrilintide has delivered substantial weight loss through a distinct mechanism and has shown a favourable safety profile. We are encouraged by these first phase 3 results for a next-generation amylin analogue and look forward to exploring cagrilintide further in the RENEW programme.”