Summary: In adults with overweight or obesity and type 2 diabetes, once-weekly cagrilintide-semaglutide (CagriSema) produced substantially greater weight loss than placebo and improved glycaemic target attainment over 68 weeks. Gastrointestinal adverse events were frequent, and cardiovascular outcomes were not assessed.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1206 adults in 12 countries with BMI >=27 kg/m2, type 2 diabetes, and baseline HbA1c 7-10%; 68-week phase 3a double-blind RCT. |
| Intervention | Once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg with lifestyle intervention (n=904). |
| Comparison | Matching placebo plus lifestyle intervention (n=302). |
| Outcome | Mean weight change -13.7% versus -3.4%; estimated difference -10.4 percentage points (95% CI -11.2 to -9.5; P<0.001). HbA1c <=6.5% was achieved by 73.5% versus 15.9%. GI events occurred in 72.5% versus 34.4%. |
CagriSema in T2D (REDEFINE 2)
Phase 3a RCT - T2D + overweight or obesity - 68 weeks
CagriSema produced 13.7% mean weight loss and substantially greater HbA1c target attainment than placebo in adults with type 2 diabetes and overweight or obesity.
Expert Commentary
REDEFINE 2 demonstrates that CagriSema can produce double-digit mean weight loss while also markedly improving glycaemic target attainment in adults with type 2 diabetes. The 10.4-percentage-point placebo-adjusted weight difference is large for this population, in whom weight loss is often more modest than in people without diabetes. Achieving HbA1c of 6.5% or lower in 73.5% of participants is encouraging, although the abstract does not make HbA1c change the principal basis for treatment comparison. Gastrointestinal events were common and should be expected during counselling and dose escalation. Can I use this with my patients? Not yet unless CagriSema is approved and available in the relevant jurisdiction. If approved, it could become an option for adults with type 2 diabetes and obesity who need substantial weight reduction despite established therapy and who accept weekly injections and close tolerability review. The trial does not show fewer cardiovascular or kidney events, and it does not answer whether combination treatment is preferable to optimized semaglutide or tirzepatide for an individual patient. Manufacturer sponsorship, 68-week follow-up, and trial-level adherence limit direct prediction of long-term real-world persistence. Future comparisons should address active incretin alternatives, cost effectiveness, body composition, treatment withdrawal, and whether the additional weight loss produces durable microvascular and macrovascular benefit.
References
Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648-659. doi:10.1056/NEJMoa2502082. PMID: 40544432.