Cagrilintide and CagriSema for weight reduction and metabolic risk modification in overweight or obesity: a systematic review and meta-analysis.
This systematic review and meta-analysis pooled data from four randomized controlled trials (n = 5,023 adults with overweight or obesity) to evaluate the efficacy and safety of cagrilintide — a long-acting amylin analogue — and its combination with semaglutide (CagriSema) versus placebo. The primary outcome was percent change in body weight. The authors followed PRISMA 2020 and AMSTAR 2 guidelines and used Cochrane RoB 2 for bias assessment, with random-effects models throughout. Key findings: cagrilintide alone was associated with a mean body weight reduction of approximately 6.1% versus placebo (95% CI: −8.0% to −4.1%), and CagriSema with approximately 6.0% (95% CI: −10.6% to −1.3%). CagriSema also significantly reduced waist circumference and HbA1c; cagrilintide alone showed modest blood pressure improvements without significant glycemic effects. Adverse events were more frequent with active treatment, though discontinuation rates were comparable to placebo. Notable limitations include the small number of pooled trials (n = 4) and potential heterogeneity across study populations and durations. The authors conclude that both therapies show clinically meaningful weight loss and acceptable tolerability, positioning them as emerging options in obesity pharmacotherapy.
Why this grade: The meta-analysis pools data from multiple RCTs in human adults (n = 5,023) with pre-specified outcomes, rigorous bias assessment, and adherence to PRISMA/AMSTAR 2 standards, representing the highest tier of clinical evidence, though the small number of included trials (n = 4) introduces some uncertainty.
Background Obesity is a global health challenge associated with substantial cardiometabolic morbidity. Cagrilintide, a long-acting amylin analogue, alone or in combination with semaglutide (CagriSema), has emerged as a novel pharmacologic strategy for weight management. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of cagrilintide-based therapies in adults with overweight or obesity. Methods A systematic review and meta-analysis of randomized controlled trials was conducted according to PRISMA 2020 and AMSTAR 2. Eligible studies enrolled adults with overweight or obesity randomized to cagrilintide or CagriSema versus placebo and reported at least one efficacy or safety outcome. The primary outcome was percent change in body weight. Secondary outcomes included absolute weight change, waist circumference, blood pressure, glycated hemoglobin (HbA1c), and safety outcomes. Random-effects meta-analyses were conducted, and risk of bias was assessed using the Cochrane RoB 2 tool. Results Four trials including 5,023 participants were pooled. Cagrilintide significantly reduced percent body weight versus placebo (mean difference - 6.08%, 95% CI - 8.02 to - 4.14), as did CagriSema (- 5.98%, 95% CI - 10.64 to - 1.32). Both interventions significantly reduced absolute body weight. CagriSema produced a significant reduction in waist circumference and HbA1c, whereas cagrilintide alone showed modest blood pressure improvements without significant glycemic effects. Overall adverse events were more frequent with active treatment, but discontinuation rates were comparable to placebo. Conclusions Cagrilintide and CagriSema achieved clinically meaningful weight loss with favorable cardiometabolic effects and acceptable tolerability, supporting their role as emerging options in obesity pharmacotherapy. Supplementary information The online version contains supplementary material available at 10.1007/s40200-026-01942-3.
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