Tirzepatide versus dulaglutide cardiovascular outcomes in type 2 diabetes

Clinical trials have shown that glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, dulaglutide) reduce the incidence of major adverse cardiovascular events in patients with high cardiovascular risk and type 2 diabetes, chronic kidney disease or obesity. As a result, clinical guidelines have integrated the use of GLP-1 receptor agonists into the treatment plans of patients at high cardiovascular risk. Tirzepatide is a dual incretin agonist of GLP-1 and glucose-dependent insulinotropic polypeptide receptors, with favourable effects on glycemic control and body weight. However, its effects on cardiovascular outcomes are uncertain.To examine this issue, researchers conducted an active-comparator–controlled, double-blind, noninferiority trial. Patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg). The primary end point was a composite of death from cardiovascular causes, myocardial infarction or stroke. Patients were followed for a median of 4.0 years.The trial was designed with an event-driven approach to test for noninferiority of tirzepatide to dulaglutide. Noninferiority to dulaglutide was determined by an upper limit of < 1.05 for the 95.3% confidence interval for the hazard ratio for death from cardiovascular causes, myocardial infarction or stroke with tirzepatide as compared with dulaglutide. An upper limit of < 1.00 was considered to indicate superiority of tirzepatide over dulaglutide.Key results:The modified intention-to-treat population included 6,586 patients in the tirzepatide group and 6,579 in the dulaglutide group (mean age 64.1 years; 29.0% women; mean body-mass index 32.6; mean glycated hemoglobin level 8.4; and mean duration of diabetes 14.7 years).The median duration of exposure to the trial drug was 47.6 months in the tirzepatide group and 47.7 months in the dulaglutide group.A primary end-point event (composite of death from cardiovascular causes, myocardial infarction or stroke) occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83–1.01; p=0.003 for noninferiority; p=0.09 for superiority).No substantial differences were observed between the two treatment groups in the incidence of adverse events, serious adverse events, or adverse events that led to discontinuation of the trial drug, although more gastrointestinal adverse events were seen in the tirzepatide group.The investigators conclude that in patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction or stroke at a median follow-up of four years. This trial was limited to patients with type 2 diabetes. The authors note that a placebo-controlled cardiovascular outcomes trial of tirzepatide in patients without type 2 diabetes who have high cardiovascular risk and overweight or obesity is currently in progress.Reference:Nicholls SJ, Pavo I, Bhatt DL, et al; SURPASS-CVOT Investigators. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med 2025;393;2409-20. (accessed January 6, 2026).

Tirzepatide versus dulaglutide cardiovascular outcomes in type 2 diabetes

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