SUN-726 - Efficacy and Safety of Cagrilintide-Semaglutide for Treatment of Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background:
CagriSema, a fixed-dose combination of cagrilintide and semaglutide, has emerged as a novel therapeutic option for obesity and metabolic disease. While individual components have demonstrated efficacy in weight reduction, the incremental benefit and safety profile of the combination compared with placebo or monotherapy remain incompletely defined. This meta-analysis evaluated the efficacy and safety of CagriSema in comparison with placebo, cagrilintide alone, and semaglutide alone.

Methods:
Medline, Embase, and the Cochrane Library were systematically searched for randomized controlled trials comparing CagriSema with placebo, cagrilintide, or semaglutide. Outcomes of interest included percent change in body weight, changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and adverse events. Mean differences (MD) or odds ratios (OR), as appropriate, with 95% confidence intervals (CI) were pooled using a random-effects model.

Results:
A total of four randomized controlled trials comprising 4,751 patients were included, of whom 3,055 patients received CagriSema, 1,007 received Placebo, 333 received Cagrilintide, and 357 received Semaglutide. CagriSema was associated with a substantial reduction in percent change in body weight when compared with placebo (MD −13.85; 95% CI −20.81, −6.90; p < 0.0001), cagrilintide monotherapy (MD −7.97; 95% CI −9.63, −6.31; p < 0.0001), and semaglutide monotherapy (MD −7.76; 95% CI −10.74, −4.78; p < 0.0001). Reductions in HbA1c favored CagriSema across all comparisons; however, these differences did not reach statistical significance versus placebo (MD −0.89; 95% CI −1.88, 0.11; p = 0.08), cagrilintide (MD −0.78; 95% CI −1.79, 0.23; p = 0.13), or semaglutide (MD −0.18; 95% CI −0.42, 0.07; p = 0.16). CagriSema significantly reduced SBP compared with placebo (MD −5.53; 95% CI −8.06, −2.99; p < 0.0001). The risk of any adverse events was higher with CagriSema compared with placebo (OR 2.04; 95% CI 1.27, 3.27; p = 0.003), but did not differ significantly when compared with cagrilintide or semaglutide. Gastrointestinal adverse events were the most commonly reported.

Conclusion:
In this meta-analysis, CagriSema demonstrated superior weight loss efficacy compared with placebo and monotherapy with cagrilintide or semaglutide, along with modest improvements in systolic blood pressure. Glycemic benefits were directionally favorable but did not reach statistical significance. While gastrointestinal adverse events were more common, overall safety was comparable to monotherapy. Larger, long-term randomized trials are needed to further define the durability of benefit and risk–benefit balance of CagriSema in diverse patient populations.

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