Tirzepatide, cardiovascular outcomes and mortality in obesity and diabetes: a systematic review and meta-analysis.

AIMS: To assess the effect of tirzepatide, a glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonist, on cardiovascular outcomes and mortality in subjects with overweight/obesity, or type 2 diabetes mellitus (T2DM).

METHODS

We searched MEDLINE, Embase and CENTRAL up to January 14, 2026, selecting randomized controlled trials studying tirzepatide in adults with T2DM or overweight/obesity with a minimum follow-up of 24 weeks. We independently extracted data and assessed risk of bias and quality of evidence. We conducted meta-analysis using a fixed-effects model. Trial sequential analysis (TSA) was employed to assess if current information support definitive conclusions.

RESULTS

We included 22 trials encompassing 29,023 participants. Overall risk of bias was low. Tirzepatide was associated with a reduction in MACE (OR 0.87, 95% CI 0.79-0.94; high certainty); TSA estimated that sample size was sufficient for definitive conclusions. A dose-response association was observed, with 2.8% lower odds of MACE for every 1 mg increase in tirzepatide dose. Tirzepatide was associated with a reduction in all-cause mortality (OR 0.84, 95% CI 0.75-0.93), however no association was observed for individual components of MACE or heart failure hospitalizations.

CONCLUSIONS

Tirzepatide is associated with a significant reduction in MACE in subjects with T2DM or overweight/obesity.