N Engl J Med

ADA 2025: Amylin analog plus semaglutide delivers powerful weight loss in obesity treatment

June 25, 2025

The combination of semaglutide and cagrilintide led to substantial and clinically meaningful weight loss compared with placebo in adults with overweight or obesity, according to an international trial. The results were shared at the recent American Diabetes Association (ADA) annual meeting.

Study details: In the 68-week, phase 3a, double-blind, placebo- and active-controlled REDEFINE 1 trial (NCT05567796), 3,417 adults with overweight or obesity (BMI ≥30 or ≥27 with at least one obesity-related comorbidy) but without diabetes were randomized to receive once-weekly injections of cagrilintide 2.4 mg plus semaglutide 2.4 mg (CagriSema), semaglutide alone, cagrilintide alone, or placebo, alongside lifestyle interventions. The primary outcomes were percent weight change and achieving ≥5% weight loss at 68 weeks with CagriSema vs. placebo; ≥20%, ≥25%, and ≥30% weight loss were key secondary outcomes. Analyses followed an intention-to-treat approach, and safety was monitored.

Results: Participants receiving CagriSema achieved a mean weight reduction of 20.4% from baseline vs. 3.0% with placebo (95% confidence interval, −18.1 to −16.6; P<0.001). CagriSema recipients were significantly more likely to achieve ≥5%, ≥20%, ≥25%, and ≥30% weight loss (P<0.001 for all comparisons). GI adverse events were common (79.6%), but mostly mild to moderate and transient.

Source:

Garvey WT; REDEFINE 1 Study Group, et al. (2025, June 22). N Engl J Med. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. https://pubmed.ncbi.nlm.nih.gov/40544433/