Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo

Background: Obesity remains a major global health challenge, driving demand for effective pharmacotherapies. Cagrilintide, a once-weekly amylin receptor agonist, and its fixed-dose combination with semaglutide (CagriSema) represent novel therapeutic approaches. This systematic review and meta-analysis evaluated their efficacy and safety in adults with overweight or obesity. Methods: Four databases were searched from inception to March 2026. Eligible randomized controlled trials (RCTs) assessed Cagrilintide monotherapy or CagriSema versus placebo. Outcomes included percentage and absolute body weight change, waist circumference, blood pressure, HbA1c, and adverse events. Data were pooled using random-effects models in RevMan, with results expressed as mean differences (MD) or risk ratios (RR) with 95% confidence intervals. Results: Four RCTs encompassing 5425 participants were included. Cagrilintide monotherapy produced significant reductions in body weight (MD: -6.08%; MD: -5.89 kg) and blood pressure, without meaningful HbA1c improvement. CagriSema significantly reduced body weight (MD: -5.98%; MD: -4.68 kg), waist circumference (MD: -10.91 cm), systolic blood pressure, and HbA1c. Both treatments showed modest but statistically significant increases in adverse events. Substantial heterogeneity was observed across most outcomes. Conclusion: Cagrilintide-based therapies produce clinically meaningful weight loss and cardiometabolic improvements. CagriSema demonstrates additional glycemic benefits over monotherapy. Larger, longer-duration trials are needed to confirm long-term efficacy and safety.