Cardiovascular Outcomes With Tirzepatide Versus GLP-1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta-Analysis
Abstract
Aims: To compare cardiovascular outcomes associated with tirzepatide versus glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with overweight or obesity.
Materials and methods: 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.
Results: 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; I 2 = 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).
Conclusions: Tirzepatide was not associated with a statistically significant reduction in MACEs. Although effect…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 323 participants or records.
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