An Observational Study of Cardiovascular Outcomes of Tirzepatide vs Glucagon-Like Peptide-1 Receptor Agonists

BACKGROUND While cardiovascular benefits of tirzepatide, a glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes mellitus (T2DM) , its comparative effectiveness vs glucagon-like peptide-1 receptor agonists (GLP-1RAs) is studied in randomized controlled trials, real-world outcomes may provide critical insights. OBJECTIVES The purpose of this study was to examine the cardiovascular benefits of tirzepatide vs GLP-1RA in people living with overweight or obesity, with T2DM, age >= 40 years, , pre-existing ischemic heart disease (IHD). METHODS A retrospective cohort analysis of de-identified, aggregate patient data from the TriNetX research network was conducted. People with T2DM, age >= 40 years, pre-existing IHD, and body mass index >= 25 kg/m(2) receiving either tirzepatide or GLP-1RA were identified and divided into 2 groups (tirzepatide vs GLP-1RA). After propensity score matching, Cox-proportional HRs were used to compare efficacy and safety outcomes during 1-year follow-up. RESULTS Among 47,719 adults, 753 received tirzepatide, and 46,966 were on GLP-1RA. After propensity score matching, each group had 751 adults (mean age 59.9 f 8.9 years, 46.5% females, 74.8% White adults in the tirzepatide group). Treatment with tirzepatide was associated with lower primary composite outcomes of acute myocardial infarc- tion, ischemic stroke, and all-cause mortality (HR: 0.60, 95% CI: 0.43-0.84, P < 0.001). Individually, acute myocardial infarction (HR: 0.59, 95% CI: 0.38-0.91) and all-cause mortality (HR: 0.35, 95% CI: 0.14-0.88, P = 0.001) were also found to be favorable in the tirzepatide group. CONCLUSIONS Tirzepatide use is associated with better outcomes in adults aged 40 years or older with T2DM, body mass index >= 25 kg/m(2), 2 , pre-existing IHD. (JACC Adv. 2025;4:101740) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).