CagriSema achieves >20% weight loss in adults with obesity.

The REDEFINE 1 trial, published in the New England Journal of Medicine, evaluated the efficacy and safety of the combination therapy cagrilintide–semaglutide (CagriSema) in adults with overweight or obesity. This randomized, double-blind, phase 3a trial included 3,417 participants without diabetes and a BMI ≥30 (or ≥27 with at least one obesity-related complication). Participants received CagriSema (2.4 mg of each agent weekly), semaglutide alone, cagrilintide alone, or placebo over 68 weeks, in addition to lifestyle interventions.

Key efficacy outcomes:

• The mean weight loss with CagriSema was –20.4% compared to –3.0% with placebo (difference: –17.3 percentage points; 95% CI, –18.1 to –16.6; P<0.001).
• Confirmatory secondary endpoints showed that 53.6% of participants in the CagriSema group achieved ≥20% weight loss, and 19.3% achieved ≥30% loss.
• In a DXA-assessed subgroup, 67% of total weight loss was fat mass, with favorable preservation of lean soft tissue.
• Improvements in systolic blood pressure (−9.9 mmHg vs. −3.2 mmHg placebo), waist circumference (−17.5 cm vs. −4.0 cm), lipid profile, inflammatory markers, and physical function were also observed.
• Among participants with prediabetes, 87.7% receiving CagriSema reverted to normoglycemia versus 32.2% in the placebo group.

Safety profile:

• Adverse events were reported in 92.3% of the CagriSema group versus 82.3% with placebo; most were gastrointestinal (nausea, diarrhea, vomiting), mild to moderate in severity, and peaked during dose escalation.
• Serious adverse events occurred in 9.8% of CagriSema users, with two deaths (suicide and cancer of unknown primary).

The study concludes that the fixed-dose combination of cagrilintide and semaglutide offers substantial and clinically meaningful weight loss in people with overweight or obesity, exceeding the results of monotherapy and with acceptable tolerability.

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