Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials.

Network meta-analysis of randomized controlled trials

“This network meta‐analysis examines their comparative efficacy and safety.”

Adults with overweight or obesity without diabetes

“enrolment of adults (≥ 18 years) with overweight (body mass index [BMI] ≥ 25 kg/m2) or obesity (BMI ≥ 30 kg/m2) without DM”

34,259 participants across 25 trials

“A total of twenty‐five studies were included in the analysis, comprising 34,259 participants.”

Minimum treatment duration of 12 weeks

“evaluation of tirzepatide, semaglutide, cagrilintide or the combination of cagrilintide and semaglutide (CagriSema) at any dose with a minimum treatment duration of 12 weeks”

Gastrointestinal adverse events increased with all treatments, while serious adverse events remained comparable to placebo

“Gastrointestinal adverse events increased with all treatments (RR 1.33–1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09).”

Substantial heterogeneity across efficacy outcomes and reliance on published trial-level data

“Substantial heterogeneity was observed across efficacy outcomes (I 2 = 89.4% for percent weight change), reflecting variability in study populations, trial duration, lifestyle co‐interventions and outcome measurement methods.”