- Question
- To determine whether coadministered cagrilintide and semaglutide (CagriSema) produces clinically relevant weight loss in adults with overweight or obesity compared with placebo.
- Design
- Phase 3a, multicenter, double-blind, placebo- and active-controlled 68-week trial in which 3417 participants were randomized in a 21:3:3:7 ratio. All groups received lifestyle interventions.
- Population
- Adults without diabetes with a BMI of 30 or higher, or a BMI of 27 or higher plus at least one obesity-related complication.
- Intervention
- Semaglutide 2.4 mg combined with cagrilintide 2.4 mg, given subcutaneously once weekly after a dose-escalation period (2108 participants).
- Control
- Placebo (705 participants), semaglutide 2.4 mg alone (302), or cagrilintide 2.4 mg alone (302).
- Primary outcome
- Two coprimary end points at week 68 versus placebo: the relative change in body weight and achievement of a body-weight reduction of 5% or more from baseline.
- Results
- Estimated mean change in body weight was -20.4% with cagrilintide-semaglutide versus -3.0% with placebo (estimated difference, -17.3 percentage points; 95% CI, -18.1 to -16.6; P<0.001). Participants on the combination were more likely to reach weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons).
- Safety
- Gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation, or abdominal pain) affected 79.6% with the combination and 39.9% with placebo; they were mainly transient and mild to moderate in severity.
- Conclusion
- CagriSema provided significant and clinically relevant body-weight reductions compared with placebo in adults with overweight or obesity.
- Why it matters
- It showed that combining two agents with complementary mechanisms can achieve greater weight loss than historically seen with available drug options, broadening the outlook for pharmacological treatment of obesity.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026