Tirzepatide Bests Dulaglutide in Cardiovascular Outcomes in HF, With Stephen Nicholls, MD

Patients with atherosclerotic cardiovascular disease (ASCVD) who received treatment with tirzepatide, irrespective of prior history of heart failure (HF), were significantly less likely to experience death due to any cause or an HF event, compared to dulaglutide, according to a prespecified analysis of the SURPASS-CVOT trial.¹

These data were presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Stephen Nicholls, MD, PhD, director of the Monash Victorian Heart Institute in Melbourne, Australia, and professor of cardiology at Monash University.¹

“SURPASS-CVOT wasn’t specifically a heart failure study, but 20% of people in the trial had a prior history of heart failure,” Nicholls told HCPLive in an exclusive interview. “So, it becomes really important because we know there’s emerging data suggesting that the GLP-1 receptor agonists and tirzepatide have favorable effects on quality of life, 6-minute walk, and potential clinical events in patients with obesity-associated heart failure.”

SURPASS-CVOT was an event-driven, randomized, double-blind, active comparator, parallel-group study conducted at 640 sites across 30 countries. Patients were randomly assigned in a 1:1 ratio to either subcutaneous tirzepatide in doses up to 15 mg or dulaglutide 1.5 mg, once weekly. Patients were then followed for cardiovascular outcomes and other measures every 4 weeks for the first 24 weeks, and then every 3 months thereafter.²

Patients eligible for inclusion were required to be ≥40 years of age, have type 2 diabetes (T2D) treated with either lifestyle or glucose-lowering medications, an HbA1c value ≥7% and ≤10.5% at screening, a body mass index (BMI) ≥25 kg/m2, and established ASCVD. Patients with prior pancreatitis, clinically significant gastric emptying abnormality, acute or chronic hepatitis, and other criteria were excluded.²

A total of 13,299 patients were randomized during the trial, with a mean age of 64.1 +/- 8.8 years and a mean BMI of 32.6 +/- 5.5 kg/m2. Ultimately, tirzepatide demonstrated non-inferiority to dulaglutide, reducing major adverse cardiovascular events such as cardiovascular death, myocardial infarction, or stroke (HR, 0.92; 95% CI, 0.83-1.01) in adults with T2D and ASCVD.^1,2

In this prespecified analysis, Nicholls and colleagues highlighted the cardiovascular effects displayed in the trial, specifically in patients with and without a history of HF at baseline. Cardiovascular events included time to first occurrence of HF composite – consisting of HF events requiring hospitalization and all-cause or cardiovascular death – and individual outcomes of HF, as well as major adverse cardiovascular events.¹

Ultimately, the composite of all-cause death or HF events occurred in a substantially lower proportion of patients in the tirzepatide group (10.5% vs 12.1%; HR, 0.86; 95% CI, 0.77-0.95). Among a total of 2678 (20.3%) patients with a history of HF, more patients had a history of coronary artery disease (77.6% vs 61.8%) and prior myocardial infarction (57.8% vs 44.5%) than those without HF.¹

In patients with a history of HF, Nicholls and colleagues found HRs of 0.83 for all-cause death or HF events (95% CI, 0.7-0.99), 0.85 for cardiovascular death or HF events (95% CI, 0.7-1.03), 0.8 for cardiovascular death (95% CI, 0.63-1.02), and 0.97 for hospitalization or urgent visits for HF (95% CI, 0.73-1.27).¹

“I think the take-home message is that this is a useful therapeutic in the clinic,” Nicholls said. “It has favorable effects on a range of metabolic parameters which are superior to GLP-1 receptor agonists. It looks like it’s at least as good in terms of atherosclerotic events; if you look at heart failure events combined, there’s a more favorable effect. I think the next step is to see what that looks like in prospective trials in patients with heart failure.”

References

1. Nicholls S, D’Alessio D. Once-weekly Tirzepatide versus Dulaglutide for Heart Failure Outcomes in Patients with Type 2 Diabetes, ASCVD, and History of Heart Failure (pre-specified analysis of the SURPASS-CVOT Randomized Clinical Trial). Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10.

2. Nicholls SJ, Bhatt DL, Buse JB, et al. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J. 2024;267:1-11. doi:10.1016/j.ahj.2023.09.007