- Question
- Is tirzepatide noninferior to dulaglutide, a GLP-1 agonist with proven cardiovascular benefit, for major cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease?
- Design
- Randomized 1:1, double-blind, active-comparator noninferiority trial with 13299 patients randomized; the modified intention-to-treat population included 6586 patients on tirzepatide and 6579 on dulaglutide after 134 who did not meet inclusion criteria were excluded.
- Population
- Adults with type 2 diabetes and established atherosclerotic cardiovascular disease; mean age 64.1 years, 29.0% women, mean HbA1c 8.4%, and mean diabetes duration 14.7 years.
- Intervention
- Once-weekly subcutaneous tirzepatide, titrated from 2.5 mg up to a maximum of 15 mg or the maximum tolerated dose.
- Control
- Once-weekly subcutaneous dulaglutide 1.5 mg.
- Primary outcome
- Composite of death from cardiovascular causes, myocardial infarction, or stroke, tested for noninferiority with a margin of 1.05 for the upper limit of the 95.3% confidence interval of the hazard ratio.
- Results
- A primary end-point event occurred in 801 patients (12.2%) on tirzepatide and 862 (13.1%) on dulaglutide (HR 0.92; 95.3% CI 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority).
- Safety
- Adverse event incidence was similar between groups, with more gastrointestinal adverse events in the tirzepatide group.
- Conclusion
- In patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide for the composite of cardiovascular death, myocardial infarction, or stroke, without demonstrating superiority.
- Why it matters
- It provides cardiovascular safety evidence for the dual GIP/GLP-1 agonist tirzepatide against a GLP-1 agonist already shown to reduce cardiovascular events, in a high-risk population.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026