Amylin Injectable Cagrilintide Demonstrates Weight Loss of 11.8% in Late-Stage Trial: Novo Nordisk Update

Novo Nordisk’s investigational long-acting amylin analogue cagrilintide achieved an average weight reduction of 11.8% after 68 weeks of treatment, according to data from a new subanalysis of the phase 3 REDEFINE 1 trial presented at the European Association for the Study of Diabetes 2025 congress, held September 15-19, in Vienna.¹

Timothy Garvey, MD

Courtesy of University of Alabama at Birmingham

Study participants receiving cagrilintide lost an average of 12.5 kg compared with 2.5 kg in the placebo group, corresponding to 2.3% body weight reduction with placebo. REDEFINE participants had obesity or had overweight with at least 1 weight-related comorbidity and did not have diabetes.¹

Around one-third (31.6%) of the study's 3417 participants receiving cagrilintide achieved weight loss of 15% or more compared with approximately 1 in 20 (4.7%) of those who received placebo. When investigators analyzed the treatment effect without regard to adherence, they reported average reductions of 11.5% with cagrilintide and 3.0% with placebo, with 31.0% and 5.2% of participants, respectively, reaching the 15% or greater threshold, according to the study.¹

Favorable Tolerability Profile

“These data highlight the exciting potential of cagrilintide to offer an alternative approach for people to lose weight, achieve health-related outcomes and manage their obesity, including a favourable tolerability profile,” lead investigator Timothy Garvey, MD, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham, said in a statement.² As with other chronic diseases, he added, it is important to have a range of treatment options available in order "to address the individual needs of people with obesity, such as their own specific response to treatment.”²

During the more than 5 years of treatment, cagrilintide was generally well tolerated, according to Novo Nordisk. The most common adverse events were gastrointestinal, ie, nausea, vomiting, diarrhea, and constipation, all of which were mostly mild to moderate in intensity and improved over time. Approximately 1.0% of participants treated with cagrilintide discontinued the trial as a result of nausea vs 0.1% of those who received placebo.²

Cagrilintide is a once-weekly injectable analogue of amylin, a hormone co-secreted with insulin that regulates satiety and slows gastric emptying. Unlike currently approved GLP-1–based weight loss therapies, cagrilintide targets a distinct pathway, offering a potential complementary mechanism for obesity management (Figure).

For the double-blind, placebo- and active-controlled phase 3 REDEFINE-1 trial participants were randomly assigned to receive once-weekly cagrilintide, semaglutide, the combination CagriSema, or placebo. All participants also followed a comprehensive lifestyle intervention, for 68 weeks. The current sub-analysis focused on cagrilintide monotherapy at a dose of 2.4 mg compared to placebo.

"With the global scale of obesity, further scientific innovation and therapy options are needed to meet every individual's needs and preferences, Martin Holst Lange, Novo Nordisk chief scientific officer and executive vice president of research and development, said in a statement. "In our clinical trials, cagrilintide has provided substantial weight loss, in a distinct manner compared to approved obesity medications, and appears well-tolerated. We’re excited that these data, the first phase 3 data of a next-generation amylin therapy, show promise and we look forward to further investigating cagrilintide’s potential in the dedicated phase 3 RENEW programme.”

Novo Nordisk will initiate the phase 3 RENEW program in the fourth quarter this year to investigate the safety and efficacy of cagrilintide monotherapy in people with obesity or overweight.

References

1. Garvey WT, Kuhlman AB, Rømer J, et al. Efficacy and safety of cagrilintide 2.4 mg in adults with overweight/obesity: data from REDEFINE 1. Abstract presented at: European Association for the Study of Diabetes annual meeting 2025; September 15-19, 2025; Vienna, Austria.

2. Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into dedicated clinical programme. News release. Novo Nordisk. September 16, 2025. Accessed September 16, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html

3. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and Ssmaglutide in adults with overweight or obesity. N Engl J Med. 2025;393:635–647. doi: 10.1056/NEJMoa2502081