Tirzepatide was noninferior to dulaglutide with respect to the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke (HR 0.92) in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
RCT (n=13,299)
Double-blind
1:1
Yes
Does tirzepatide prevent a composite of death from cardiovascular causes, myocardial infarction, or stroke in patients with type 2 diabetes and atherosclerotic cardiovascular disease compared to dulaglutide?
Tirzepatide is noninferior to dulaglutide for major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
Effect estimate: HR 0.92 (95% CI 0.83-1.01)
Absolute Event Rate: 12.2% vs 13.1%
p-value: p=0.003
BACKGROUND: Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain. METHODS: We conducted an active-comparator-controlled, double-blind, noninferiority trial in which 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), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide. RESULTS: A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years. A primary end-point event 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 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group. CONCLUSIONS: Among 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. (Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.).
Multiple April 2026 media stories (>10 outlets) on tirzepatide reducing CV risk, mortality, and cardiorenal events vs dulaglutide or in post-TAVR/PCI patients; high social shares on X among cardiologists and endocrinologists; ongoing discussion of GLP-1/GIP dual agonists in CV disease.
Nicholls et al. (2025) conducted an RCT in Type 2 diabetes and atherosclerotic cardiovascular disease (n=13,299). Tirzepatide vs. Dulaglutide 1.5 mg weekly was evaluated on Composite of death from cardiovascular causes, myocardial infarction, or stroke (HR 0.92, 95% CI 0.83-1.01, p=0.003). Tirzepatide was noninferior to dulaglutide with respect to the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke (HR 0.92) in patients with type 2 diabetes and atherosclerotic cardiovascular disease.