Efficacy and Safety of CagriSema in Type 2 Diabetes: A Dose- and Comparator-Specific Systematic Review and Bayesian Meta-Analysis.
TL;DR
CagriSema provides substantial glycaemic and body-weight benefits versus placebo and is more evident for body-weight reduction, while comparative gastrointestinal tolerability and discontinuation risk remain uncertain.
Abstract
Background
CagriSema combines cagrilintide with semaglutide and may improve glycaemic control and body weight in Type 2 diabetes. We evaluated its dose- and comparator-specific efficacy and safety.
Methods
PubMed, Embase, CENTRAL and ClinicalTrials.gov were searched through 30 June 2026 for randomized controlled trials. Analyses were stratified by CagriSema dose and comparator. For HbA1c and body weight, efficacy/trial-product estimands were aligned where sufficiently reported, with treatment-policy estimates examined in sensitivity analyses. Bayesian random-effects models generated posterior medians and 95% credible intervals (CrIs).
Results
Six trials representing 4554 potentially eligible participants with Type 2 diabetes were included. Compared with placebo, CagriSema 2.4 mg produced between-group differences of -1.87 percentage points in HbA1c (95% CrI, -2.08 to -1.62) and -12.69 percentage points in percentage body-weight change (95% CrI, -13.78 to -11.61). Versus semaglutide 2.4 mg, the additional HbA1c reduction was modest and uncertain (-0.21 percentage points; 95% CrI, -0.62 to 0.11), whereas additional body-weight reduction remained probable (-5.84 percentage points; 95% CrI, -10.08 to -2.15). Gastrointestinal adverse events and adverse-event-related discontinuation were increased versus placebo (RR, 2.27 [95% CrI, 1.81 - 3.00] and 3.16 [1.50 to 6.87], respectively), while estimates versus semaglutide were less precise.
Conclusions
CagriSema provides substantial glycaemic and body-weight benefits versus placebo. Its incremental advantage over dose-matched semaglutide is more evident for body-weight reduction, while comparative gastrointestinal tolerability and discontinuation risk remain uncertain.