Cardiovascular Outcomes With Tirzepatide Versus GLP-1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta-Analysis.

Authors

João Pedro Machado Ribeiro Jacintho Silva, Bruno Viruez Nogueira, Deborah Lomelino Sartori, Juliana Rizzo Cardoso da Silva, Lucca Biagio Argenton Sciota, Oscar Inácio de Mendonça Bisneto, Wilton Francisco Gomes

Published in

Diabetes, obesity & metabolism. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

To compare cardiovascular outcomes associated with tirzepatide versus glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with overweight or obesity.
PubMed/MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched through 30 March 2026. The study was registered in PROSPERO (CRD420261354941). Randomized and observational studies comparing tirzepatide with GLP-1 receptor agonists and reporting cardiovascular outcomes were included. Data were extracted on study characteristics and outcomes using adjusted hazard ratios when available. Risk of bias was assessed using RoB 2 and ROBINS-I.
Eight studies (one randomized and seven observational) including 323 439 patients were analysed. Tirzepatide was not associated with a statistically significant reduction in major adverse cardiovascular events (MACE) compared with GLP-1 receptor agonists (HR 0.85, 95% CI 0.70-1.04; I² = 90.4%). Substantial heterogeneity was observed. Effect estimates were directionally consistent across secondary outcomes, including all-cause mortality (HR 0.90, 95% CI 0.79-1.02) and cardiovascular mortality (HR 0.88, 95% CI 0.76-1.00). In exploratory subgroup analyses, patients with type 2 diabetes showed lower estimated risks of all-cause mortality (HR 0.85, 95% CI 0.76-0.94) and heart failure (HR 0.75, 95% CI 0.58-0.97).
Tirzepatide was not associated with a statistically significant reduction in MACEs. Although effect estimates were directionally consistent across analyses, substantial heterogeneity and the predominance of observational studies limit causal interpretation. Further randomized trials are needed to clarify the comparative cardiovascular effects of tirzepatide.

PMID:
42410309
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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