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
- 1Universidade Federal do Rio Grande do Sul
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.
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BibTeX
@misc{diefenthaeler2026cagrisema,
title = {{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}},
author = {B. M. Diefenthaeler and L. E. d. Canto and G. M. Pretto and H. C. Malta and G. L. Noll and L. d. O. Magalhaes and G. G. d. Santos and F. Gerchman},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.26366916},
url = {https://www.medrxiv.org/content/10.64898/2026.10.30.26366916v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - 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
AU - B. M. Diefenthaeler
AU - L. E. d. Canto
AU - G. M. Pretto
AU - H. C. Malta
AU - G. L. Noll
AU - L. d. O. Magalhaes
AU - G. G. d. Santos
AU - F. Gerchman
PY - 2026
DA - 2026/10/30
PB - medRxiv
DO - 10.64898/2026.10.30.26366916
UR - https://www.medrxiv.org/content/10.64898/2026.10.30.26366916v1
AB - 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.
ER -