Tirzepatide was not associated with a statistically significant reduction in MACEs compared to GLP-1 receptor agonists in adults with overweight or obesity.
Meta-Analysis
Does tirzepatide reduce major adverse cardiovascular events compared to GLP-1 receptor agonists in adults with overweight or obesity?
In adults with overweight or obesity, tirzepatide did not significantly reduce MACE compared to GLP-1 RAs, though exploratory analyses suggest potential benefits in patients with type 2 diabetes.
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: = 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 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.
Silva et al. (Mon,) conducted a meta-analysis in Overweight or obesity. Tirzepatide vs. GLP-1 receptor agonists was evaluated on MACEs. Tirzepatide was not associated with a statistically significant reduction in MACEs compared to GLP-1 receptor agonists in adults with overweight or obesity.
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