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

CagriSema 2.4/2.4 mg resulted in greater weight loss than 1.0/1.0 mg, but the reduction was below the clinically meaningful threshold, and there was no significant benefit for HbA1c levels.

Summary and findings

This study compared the efficacy and safety of cagrilintide–semaglutide (CagriSema) at two maintenance doses, 2.4/2.4 mg and 1.0/1.0 mg, in adults with type 2 diabetes. The primary outcomes included body weight reduction and glycated hemoglobin (HbA1c) levels. Results indicated a greater reduction in body weight with the higher dose but no statistically significant difference in HbA1c levels.

Abstract

<h4>Background</h4> 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. <h4>Methods</h4> 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). <h4>Results</h4> 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. <h4>Conclusions</h4> 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. <h4>Registration</h4> CRD420261545958 (registered 10/21/2026).

Limitations

Not reported in abstract.

Elsewhere in the Cagrilintide (AM833) corpus