Dose-specific efficacy and safety of cagrisema in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Background CagriSema, a fixed-dose combination of cagrilintide and semaglutide, is a promising option for type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis evaluating its efficacy and safety versus placebo and active comparators. Methods We searched PubMed, Embase via Elsevier, the Cochrane Library, and ClinicalTrials.gov to June 2026 for randomized controlled trials comparing CagriSema with placebo, semaglutide, or cagrilintide. Random-effects meta-analyses calculated mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes with 95% confidence intervals (CIs). Risk of bias was assessed using Cochrane RoB 2 and certainty using GRADE. Results Six RCTs (4,805 participants) were included. Compared with controls, CagriSema significantly reduced HbA1c (MD − 1.01%; 95% CI − 1.44 to − 0.57) and fasting plasma glucose (MD − 1.41 mmol/L; 95% CI − 2.08 to − 0.75) at 2.4 mg, while 1 mg also reduced HbA1c (MD − 0.99%; 95% CI − 1.73 to − 0.25) and fasting plasma glucose (MD − 1.04 mmol/L; 95% CI − 1.82 to − 0.26). CagriSema 2.4 mg also reduced body weight (MD − 8.31%; 95% CI − 10.58 to − 6.04), waist circumference (MD − 7.32 cm; 95% CI − 10.02 to − 4.61), and systolic blood pressure (MD − 4.30 mmHg; 95% CI − 7.41 to − 1.19), while corresponding effects with 1 mg were − 8.76% (95% CI − 13.16 to − 4.36), − 5.66 cm (95% CI − 9.33 to − 1.99), and − 4.73 mmHg (95% CI − 9.13 to − 0.33), respectively. Serious adverse events did not differ significantly between CagriSema and comparators at either dose. Gastrointestinal adverse events and treatment discontinuation were more frequent with 2.4 mg, whereas 1 mg had a smaller increase in gastrointestinal adverse events without significantly increasing discontinuation. GRADE certainty ranged from low to high. Conclusions CagriSema provides improvements in glycemic control, body weight, and cardiometabolic risk factors, with an acceptable safety profile. Long-term randomized studies are needed to confirm safety and durability. Clinical trial number Not applicable.