SURPASS-CVOT Results: How Does Tirzepatide Stack Up Against Dulaglutide for Cardiovascular Health?
Published: December 17, 2025 | Source: New England Journal of Medicine
Tirzepatide, the dual GIP and GLP-1 receptor agonist, has already made waves for its potent effects on glycemic control and weight loss. But for patients with Type 2 Diabetes (T2D), cardiovascular safety is paramount.
The highly anticipated results of the SURPASS-CVOT trial have arrived, offering a head-to-head comparison between Tirzepatide and Dulaglutide. Here is the breakdown of what the study found and what it means for the future of diabetes management.
Study Overview: The Setup
The SURPASS-CVOT trial was designed to answer a critical question: Is Tirzepatide non-inferior (at least as good as) to Dulaglutide regarding cardiovascular outcomes?
This was an active-comparator trial, meaning Tirzepatide wasn’t just tested against a placebo; it was tested against Dulaglutide (1.5 mg), a drug already proven to reduce the incidence of cardiovascular events.
- Population: 13,299 patients (Modified ITT ~6,580 per group).
- Patient Profile: Adults with Type 2 Diabetes and established atherosclerotic cardiovascular disease (ASCVD).
- Intervention: Weekly subcutaneous Tirzepatide (up to 15 mg).
- Comparator: Weekly subcutaneous Dulaglutide (1.5 mg).
- Primary Endpoint: 3-point MACE (Composite of death from cardiovascular causes, myocardial infarction, or stroke).
Key Findings: The Numbers
The trial met its primary objective. Tirzepatide demonstrated non-inferiority to Dulaglutide, though it did not reach statistical significance for superiority.
1. Primary Endpoint (MACE-3)
- Tirzepatide Group: 801 events (12.2%)
- Dulaglutide Group: 862 events (13.1%)
- Hazard Ratio (HR): 0.92 (95.3% CI, 0.83 to 1.01)
2. Statistical Significance
- Non-inferiority: Met ($P=0.003$). This confirms Tirzepatide is safe relative to an established cardioprotective drug.
- Superiority: Not Met ($P=0.09$). While there was a numerical trend favoring Tirzepatide (an 8% relative risk reduction), it did not cross the threshold for statistical superiority.
Note on Demographics: The average patient was 64 years old with a diabetes duration of nearly 15 years and a starting HbA1c of 8.4%.
Safety Profile
The safety data was consistent with known side effects of incretin-based therapies.
- Overall Adverse Events: Similar rates between both groups.
- Gastrointestinal Issues: More frequent in the Tirzepatide group compared to the Dulaglutide group.
The Bottom Line
The SURPASS-CVOT trial provides crucial reassurance regarding the cardiovascular safety of Tirzepatide. By proving non-inferiority to Dulaglutide—a rigorous active comparator—Tirzepatide has solidified its position in the treatment arsenal for high-risk Type 2 Diabetes patients.
While the trial missed the mark for proving superiority, the hazard ratio of 0.92 suggests a favorable profile that aligns with the potent metabolic benefits (weight and glucose lowering) observed in previous studies.