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.