Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Obesity is a complex chronic disease requiring effective long-term management. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of cagrisema and cagrilintide monotherapy compared with semaglutide in individuals with obesity. METHODS: We searched MEDLINE, Embase, Scopus, Cochrane, and ClinicalTrials.gov for randomized controlled trials accessing cagrisema or cagrilintide versus semaglutide for weight loss. Efficacy outcomes were percentage change in body weight, absolute change in body weight, fasting plasma glucose, HbA1c, and BMI. Lipid parameters included total cholesterol, LDL-C, HDL-C, VLDL-C, and triglycerides. A random-effects model was used to estimate mean differences (MD) or risk ratios (RR) with 95% CIs. RESULTS: Three RCTs (n = 3545) were included. Cagrisema produced significantly greater percentage [MD -7.47% (95% CI: -10.58, -4.36); p < 0.001] and absolute [MD -7.60 kg (95% CI: -10.33, -4.86); p < 0.001] weight loss than semaglutide. Cagrilintide monotherapy weight loss was comparable to semaglutide. Lipids parameters were mostly similar between groups, though LDL-C was modestly higher with combination therapy versus semaglutide [MD 0.29 mmol/L (95% CI: 0.02, 0.55); p = 0.03]. Overall and serious adverse events were comparable between cagrisema and semaglutide, but combination therapy increased administration-site conditions [RR 3.27 (95% CI: 1.27, 8.46)] and nausea [RR 1.64 (95% CI: 1.01, 2.66)]. Cagrilintide monotherapy had a higher risk of serious adverse events [RR 1.83 (95% CI: 1.03, 3.24)] compared to semaglutide. CONCLUSION: Cagrisema is more effective than semaglutide in reducing weight and increasing glycemic control. Cagrisema is safe and has a comparable side effect profile to currently accepted treatments. This regimen has enormous potential in dual-agonist therapy for obese patients.