Cagrilintide and CagriSema achieve clinically meaningful weight loss and cardiometabolic improvements in overweight/obesity

Obesity is a pervasive global health challenge, strongly linked to significant cardiometabolic morbidity, including type 2 diabetes mellitus and cardiovascular disease. Current standard-of-care often falls short in achieving sustained weight loss and comprehensive metabolic improvements. Cagrilintide, a long-acting amylin analogue, and its combination with semaglutide (a GLP-1 receptor agonist) as CagriSema, represent novel pharmacologic strategies. This meta-analysis evaluates their efficacy and safety to address the need for more effective, well-tolerated obesity treatments.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted, adhering to PRISMA 2020 and AMSTAR 2 guidelines. The analysis pooled data from four trials involving 5,023 participants diagnosed with overweight or obesity. Studies compared cagrilintide or CagriSema against a placebo arm. The primary outcome assessed was the percent change in body weight. Secondary outcomes included absolute weight change, waist circumference, blood pressure, and glycated hemoglobin (HbA1c). Risk of bias for included studies was evaluated using the Cochrane RoB 2 tool.

Both cagrilintide and CagriSema demonstrated significant reductions in body weight compared to placebo. Cagrilintide monotherapy reduced percent body weight by a mean difference of -6.08% (95% CI -8.02 to -4.14). Similarly, CagriSema achieved a mean reduction of -5.98% (95% CI -10.64 to -1.32) in percent body weight. Both interventions also significantly reduced absolute body weight. Beyond weight loss, CagriSema produced significant reductions in waist circumference and HbA1c levels, indicating broader metabolic benefits. Cagrilintide alone showed modest improvements in blood pressure but did not significantly impact glycemic markers. Overall, active treatments were associated with more frequent adverse events, though discontinuation rates remained comparable to placebo. The findings support their role as effective options in obesity pharmacotherapy.

Cagrilintide significantly reduced percent body weight versus placebo by -6.08% (95% CI -8.02 to -4.14), while CagriSema achieved a -5.98% reduction (95% CI -10.64 to -1.32).