Maximizing weight loss with cagrisema: a systematic review and GRADE-assessed meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of CagriSema, a fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, compared with placebo, cagrilintide, or semaglutide monotherapy in overweight or obese individuals. A systematic review and meta-analysis was conducted in accordance with PRISMA and Cochrane guidelines. Seven randomized controlled trials (RCTs) (n = 8,069) were included. Pooled analyses were performed using random-effects models, including subgrouping based on type 2 diabetes status. Risk of bias was assessed with RoB 2, and certainty of evidence was graded with GRADE. CagriSema produced significantly greater weight loss than semaglutide (MD = -7.58 kg; 95% CI = -10.30 to -4.86; p < 0.00001), cagrilintide (MD -9.24 kg; 95% CI -10.46 to -8.02, p < 0.00001), and placebo (MD = -13.99 kg; 95% CI = -18.38 to -9.61; p < 0.00001). Glycemic outcomes were heterogeneous, but lipid parameters improved versus placebo. Adverse events were primarily gastrointestinal and injection-site reactions, with no increase in serious adverse events. CagriSema provides substantial and clinically meaningful weight reduction with a favorable safety profile. Importantly, it demonstrates superior efficacy to both cagrilintide and semaglutide, highlighting its therapeutic potential. Future large-scale trials are required to confirm long-term safety and durability, especially given its clear advantage over semaglutide in reducing body weight.