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Adipose Tissue_Appetite_and Obesity

SUN-732 - Safety and Efficacy of Cagrilintide - Semaglutide Combination in Adults with Obesity: An Updated GRADE-Assessed Systematic Review and Meta-Analysis of Rcts

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Daniah Rizwan, MD: No financial relationships to disclose


Background: The combination of cagrilintide and semaglutide, known as CagriSema, shows significant promise for weight loss in obese adults, providing better results than either drug alone by targeting multiple appetite pathways. The objective is to systematically evaluate the efficacy and safety of the cagrilintide-semaglutide combination in obese adults by synthesizing evidence from randomized controlled trials using the GRADE methodology.
Methodology: Embase, PubMed, Cochrane Library, and ClinicalTrials.gov were searched through December 2025 to identify randomized controlled trials evaluating the cagrilintide–semaglutide combination in obese adults; Pooled analyses of efficacy outcomes (weight loss, HbA1c) and safety outcomes (adverse events, serious adverse events, and discontinuation due to gastrointestinal adverse events) were performed using random-effects models in R (Metafor package), with heterogeneity assessed using the I² statistic and certainty of evidence classified using GRADE.

Results: CagriSema led to significantly greater weight loss compared to placebo and active comparators, with a mean difference of −8.44% (95% CI −12.88 to −4.00; I² = 0%). The odds of ≥5% weight loss were significantly higher with CagriSema (RR 2.86, 95% CI 1.89-4.33; I² = 0%), while the effect was significantly higher for ≥20% weight loss (RR 29.74, 95% CI 14.12-62.67; I² = 0%), with significant subgroup differences (P < 0.05). 0.0001).
In participants with type 2 diabetes, Cagrisema improved glycemic control, reducing HbA1c by -1.40 percentage points compared with placebo. Gastrointestinal adverse events were more common with CagriSema (RR 1.54, 95% CI 1.19-2.00; I² = 90.5%); However, serious adverse events were not increased (RR 1.11, 95% CI 0.66–1.88). Discontinuations due to adverse events occurred more frequently with Cagrisema (RR 1.90, 95% CI 1.10-3.26; I² = 0%).

Conclusion: The cagrilintide-semaglutide combination demonstrated superior efficacy for weight loss and glycemic improvement compared to placebo or monotherapy, with a greater chance of achieving a clinically meaningful weight loss threshold, although at the expense of gastrointestinal adverse events and treatment discontinuation.

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