SURPASS-CVOT Subgroup Analysis Finds Lower Death and Heart-Failure Event Rates for Tirzepatide Versus Dulaglutide in Patients With Prior Heart Failure

European Journal of Preventive Cardiology, a journal of the European Society of Cardiology, published a new analysis online October 15, 2026 drawn from SURPASS-CVOT, a completed head-to-head cardiovascular outcomes trial comparing the GIP/GLP-1 dual agonist tirzepatide with the GLP-1 receptor agonist dulaglutide. The analysis was led by Stephen J. Nicholls of the Victorian Heart Institute at Monash University, with co-authors from Eli Lilly and Company and academic cardiology and endocrinology centers in the United States, Europe, Australia, Brazil, and Canada.

SURPASS-CVOT (ClinicalTrials.gov NCT04255433) enrolled adults with type 2 diabetes and established atherosclerotic cardiovascular disease, randomizing them to tirzepatide at doses up to 15 mg weekly or dulaglutide at 1.5 mg weekly, with an average follow-up of about 4 years. The trial's primary results, establishing overall cardiovascular safety non-inferiority for tirzepatide compared with dulaglutide, were posted to ClinicalTrials.gov on July 8, 2026. The new publication is a separate, exploratory analysis that divides the trial population by whether participants had a history of heart failure at enrollment, since the effect of either drug on heart failure outcomes specifically had not been reported by that history.

Of the trial's participants, 20.3% had a documented history of heart failure before enrollment. This subgroup had more coronary artery disease and more prior heart attacks than participants without heart failure, and experienced higher rates of cardiovascular events and death overall during the trial, regardless of which drug they received.

Within each subgroup, the authors compared tirzepatide with dulaglutide on several outcome measures. For the composite of all-cause death or hospitalization or urgent visit for heart failure, the hazard ratio for tirzepatide versus dulaglutide was 0.83 (95% CI 0.70 to 0.99) among patients with prior heart failure and 0.88 (95% CI 0.78 to 1.00) among those without. For cardiovascular death or heart-failure hospitalization/urgent visit, the hazard ratio was 0.85 (95% CI 0.70 to 1.03) with heart failure and 0.96 (95% CI 0.83 to 1.12) without. For the three-component MACE endpoint (cardiovascular death, heart attack, or stroke), the hazard ratio was 0.90 (95% CI 0.76 to 1.08) with heart failure and 0.93 (95% CI 0.83 to 1.04) without; for the four-component MACE endpoint, which adds coronary revascularization, the hazard ratio was 0.81 (95% CI 0.69 to 0.95) with heart failure and 0.91 (95% CI 0.83 to 1.00) without. The authors also reported that patient-reported quality of life scores, using the APPADL and EQ-5D-5L instruments, improved in both subgroups and were higher among participants on tirzepatide.

The authors characterize the findings as an exploratory analysis built on a trial that was designed and powered to answer a cardiovascular safety non-inferiority question, not a dedicated heart-failure outcomes trial, and describe the heart-failure subgroup comparisons as hypothesis-generating. The paper's conflict-of-interest statement discloses that several co-authors, including the lead statistician and multiple named investigators, are employees and stockholders of Eli Lilly and Company, which markets tirzepatide as Mounjaro and Zepbound; other co-authors disclosed research funding, consulting fees, or advisory roles with Eli Lilly, Novo Nordisk, and other drugmakers.

Tirzepatide and dulaglutide are both already approved by the FDA and the European Medicines Agency, tirzepatide as Mounjaro for type 2 diabetes and Zepbound for chronic weight management, and dulaglutide as Trulicity for type 2 diabetes. This exploratory subgroup analysis does not change either drug's approved status in any market and is not a recommendation to switch therapy. It reports an association within a prespecified subgroup of a completed trial, not a new clinical trial in heart-failure patients specifically, and is not treatment or dosing guidance; cardiovascular care decisions should be made with a qualified clinician.