CagriSema: what the 2025 REDEFINE trials showed
Two NEJM Phase 3a papers in June 2025 tested cagrilintide plus semaglutide. A 2026 head-to-head later missed non-inferiority versus tirzepatide.
CagriSema combines two peptides: cagrilintide, an amylin analog, and semaglutide, a GLP-1 receptor agonist. In June 2025 the *New England Journal of Medicine* published the pivotal Phase 3a pair.
REDEFINE 1
Adults with overweight or obesity, without diabetes, were randomized to the combination, each drug alone, or placebo for 68 weeks. Cagrilintide–semaglutide produced larger weight reductions than placebo. Gastrointestinal adverse events were common, as they are with incretin drugs.
REDEFINE 2
Adults with type 2 diabetes and BMI of 27 or higher received the combination or placebo for 68 weeks. Weight fell more than on placebo, and more participants reached an HbA1c of 6.5% or lower. GI events again dominated the safety story.
After the papers
A later open-label REDEFINE 4 comparison with tirzepatide (reported 2026) did not meet its non-inferiority weight-loss goal. That does not erase REDEFINE 1–2; it shows how fast this class is still being compared.
Bottom line
Evidence ladder: Human RCT. These are investigational combination products in regulated trials — not the same thing as mixing research-chemical amylin and GLP-1 vials.
Sources
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