In patients with obesity and heart failure with preserved ejection fraction (HFpEF), weekly treatment with tirzepatide over approximately two years reduced the risk of worsening heart failure events, based on findings from the SUMMIT trial presented at AHA 2024 and simultaneously published in NEJM. Study authors also noted improvements in health status and exercise tolerance.

The study from Milton Packer, MD, FACC; Michael R. Zile, MD, FACC; and Christopher M. Kramer, MD, FACC, et al., randomized 731 patients from 129 centers in nine countries to receive tirzepatide up to 15 mg subcutaneously weekly (n=364) or placebo (n=367) for a median of two years. All participants had HFpEF and a BMI of greater than 30 kg/m2 and exhibited substantial health status limitations based on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and 6-minute walking distance (6MWD). Nearly 50% of participants were also hospitalized or had visited and urgent care for worsening heart failure in the 12 months prior to the study.

The primary endpoint of cardiovascular death or worsening heart failure events occurred in 36 patients in the tirzepatide group compared with 56 patients in the placebo group, (hazard ratio, 0.62; 95% CI: 0.41–0.95; p=0.026). Broken down, researchers said that worsening heart failure events were less frequent in the tirzepatide group, but no significant difference was observed in cardiovascular death.

In other findings, both KCCQ-CSS and 6MWD increased more among patients in the tirzepatide group than those in the placebo group at 52 weeks. Patients in the tirzepatide group also experienced a greater loss of body weight (by 11.6% [–12.9 to –10.4]) and saw a decrease in a decrease in and high sensitivity C-reactive protein.

"The SUMMIT trial showed that the combined GIP/GLP1 receptor agonist Tirzepatide reduces the combined endpoint of death and heart failure events in patients with obesity-related [HFpEF]," says Kramer. "This expands the indication for this drug beyond weight loss and treating diabetes. Cardiologists now have an ever-expanding armamentarium to treat HFpEF."