Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression.
This systematic review and meta-analysis evaluated the efficacy and safety of cagrisema (a fixed-ratio combination of the amylin analogue cagrilintide and the GLP-1 receptor agonist semaglutide) and cagrilintide monotherapy compared with semaglutide monotherapy for obesity management. Researchers searched five major databases and ClinicalTrials.gov, ultimately including three randomized controlled trials comprising 3,545 participants. Using a random-effects model, the study found that cagrisema produced statistically significantly greater reductions in percentage body weight (mean difference –7.47%, 95% CI: –10.58 to –4.36) and absolute body weight compared with semaglutide alone. Cagrisema also demonstrated superior improvements in glycemic markers, including fasting plasma glucose and HbA1c, and in BMI. Lipid parameters and safety profiles were reported as broadly comparable between groups. The authors concluded that cagrisema showed greater weight-loss efficacy and glycemic benefit than semaglutide, with an acceptable tolerability profile. Limitations include the small number of included trials (n=3), potential heterogeneity across trial designs, and the relatively short follow-up durations typical of early-phase RCTs in this therapeutic area.
Why this grade: While based on RCT data in humans, the pooled analysis includes only three trials (n=3,545), limiting precision and generalizability, which precludes a strong-human grade.
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 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.
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