Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established therapies for cardiovascular risk reduction in type 2 diabetes mellitus (T2DM). With the introduction of tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, questions have emerged regarding its comparative cardiovascular efficacy. A systematic review and frequentist network meta-analysis published in Cardiovascular Diabetology evaluated cardiovascular outcomes associated with tirzepatide and GLP-1RAs.

Eligible randomized controlled trials enrolled adults with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk and reported major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. Eleven trials met the inclusion criteria, including 10 GLP-1RA trials and the SURPASS-CVOT trial evaluating tirzepatide.

In the class-level analysis, tirzepatide was associated with lower risk of MACE compared with placebo (HR 0.79, 95% CI 0.69-0.91), along with lower cardiovascular mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97). Formal statistical comparisons between tirzepatide and the GLP-1RA class were not feasible within the network meta-analysis framework, although point estimates numerically favored tirzepatide versus placebo. At the agent level, tirzepatide was associated with lower MACE risk compared with placebo (HR 0.81, 95% CI 0.70–0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97). Subgroup and sensitivity analyses did not materially alter point estimates.

These findings indicate that tirzepatide was associated with cardiovascular risk reductions compared with placebo and showed comparable efficacy to individual GLP-1 RAs in adults with T2D and elevated cardiovascular risk.