CagriSema 2.4/2.4 mg versus CagriSema 1.0/1.0 mg in adults with type 2 diabetes: a dose-comparison systematic review and meta-analysis of randomized controlled trials
Year: 2026
Type: preprint
Study designs: Systematic Review, Meta-Analysis
Abstract: Background Once-weekly cagrilintide–semaglutide (CagriSema) has been evaluated at two maintenance doses, 2.4/2.4 mg and 1.0/1.0 mg, in type 2 diabetes (T2DM), but they have not been directly compared. We compared their efficacy and safety. Methods We searched PubMed, Embase, and Cochrane CENTRAL for randomized controlled trials (RCTs) comparing both doses. Contrasts derived from arm-level estimates were pooled using random-effects models. Primary outcomes were interpreted against prespecified minimally important differences (MIDs) of 3 percentage points (pp) for body weight and 0.3 pp (3.3 mmol/mol) for glycated hemoglobin (HbA1c). Results Three trials (1,506 participants) were included. CagriSema 2.4/2.4 mg produced a greater reduction in body weight (mean difference [MD] −2.07 pp; 95% confidence interval [CI] −2.91 to −1.24), with the entire CI below the MID, and higher proportions achieving reductions of ≥10% (64.9% vs. 55.1%) and ≥15% (41.9% vs. 30.9%). The difference in HbA1c was not statistically significant (MD −0.16 pp [−1.7 mmol/mol]; 95% CI −0.43 to 0.10 [−4.7 to 1.1 mmol/mol]). The higher dose increased gastrointestinal disorders (64.8% vs. 53.2%; risk ratio 1.22; 95% CI 1.12 to 1.32), without differences in serious adverse events or adverse events leading to treatment discontinuation. Certainty of evidence was high for body weight and moderate for HbA1c. Conclusions CagriSema 2.4/2.4 mg provided additional weight loss smaller than the MID, no clear HbA1c benefit, and more gastrointestinal adverse events than 1.0/1.0 mg, supporting individualized dose selection. Registration CRD420261545958 (registered 10/21/2026).
Source: medRxiv
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225108395