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CagriSema Yields Nearly 16% Weight Loss in Phase 3 REDEFINE 2 Trial
The pivotal trial showed superior weight loss to placebo at 68 weeks but fell short of ≥25% weight loss initially expected by Novo Nordisk.
CagriSema, a fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, achieved superior weight loss to placebo in adults with obesity or overweight and type 2 diabetes (T2D) in the Phase 3 REDEFINE 2 trial.
As announced by Novo Nordisk on March 10, 2025, these topline results showed the treatment effect of CagriSema led to a weight reduction of nearly –16%, compared with –3% for placebo, in people with overweight or obesity, if all individuals adhered to treatment.
“The REDEFINE 2 results confirmed the superior efficacy of CagriSema in people with overweight or obesity and T2D,” said Martin Holst Lange, executive vice president of development at Novo Nordisk. “We look forward to bringing this second pivotal trial to regulatory authorities with the aim of making this next-generation therapy available to the millions of patients in need.”
Obesity has become a notable public health epidemic in the past 5 decades, with the economic burden estimated to be nearly $100 billion annually in the US. Reports from the Centers for Disease Control and Prevention (CDC) suggested one-third of adults and approximately 17% of adolescents in the US are considered obese.
Once-weekly CagriSema is under investigation in the REDEFINE trial program for overweight or obesity and the REIMAGINE program for T2D.
The second of two pivotal Phase 3 trials, REDEFINE 2 trial enrolled 1206 adults with T2D and obesity or overweight and a mean baseline body weight of 102 kg. Based on a flexible protocol, the trial allowed patients to modify their CagriSema dosing during the trial—nearly 62% of patients were on the highest dose at 68 weeks.
The trial met its primary endpoint, with CagriSema showing a statistically significant and superior weight loss at 68 weeks versus placebo treatment. Upon analysis, CagriSema demonstrated –15.7% weight loss, compared with –3.1% with placebo. A weight loss of ≥5% after 68 weeks was achieved by 89.7% of patients on CagriSema, compared with 30.3% for placebo.
Application of the treatment policy estimand showed CagriSema treatment, irrespective of adherence, led to a superior weight loss of –13.7%, compared with –3.4% with placebo. The combination drug was safe and well-tolerated, with the most common adverse events being gastrointestinal. Novo Nordisk indicated most were mild to moderate and lessened over time, consistent with the GLP-1 receptor agonist medication class.
Previously reported topline data from the pivotal REDEFINE 1 trial showed a superior weight loss of nearly –23% after 68 weeks with CagriSema versus placebo or each drug alone but fell short of the ≥25% expected by the company. With a flexible dosing protocol, only 57.3% of the CagriSema population were on the highest dose at the end of the trial.
In REDEFINE 1, nearly 40% of patients treated with CagriSema achieved a ≥25% weight loss at the end of 68 weeks. Irrespective of adherence, CagriSema’s treatment effect showed a superior weight loss of –20.4%, compared with –11.5% for cagrilintide 2.4 mg, –14.9% for semaglutide 2.4 mg and –3.0% for placebo.
In the release, Novo Nordisk announced its intention to file for regulatory approval of CagriSema in the first quarter of 2026, with plans to present the full results from REDEFINE 1 and REDEFINE 2 at a scientific meeting in 2025.
References
CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial. Novo Nordisk. March 10, 2025. Accessed March 10, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915294.
Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459357/
Iapoce C. CagriSema achieves 22.7% weight loss in phase 3 redefine 1 trial. HCP Live. December 20, 2024. Accessed March 10, 2025. https://www.hcplive.com/view/cagrisema-achieves-22-7-weight-loss-in-phase-3-redefine-1-trial.
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