Tirzepatide successful in phase III study showing benefit in adults with heart failure with preserved ejection fraction and obesity

Tirzepatide demonstrated statistically significant improvements in both primary endpoints with a reduction in the risk of heart failure outcomes, assessed as a composite endpoint, and improvements in heart failure symptoms and physical limitations, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS),i compared with placebo.

In this phase III SUMMIT trial, Lilly's tirzepatide reduced the risk of adverse HF outcomes—such as hospitalization or cardiovascular death—by 38% compared with placebo. The study enrolled 731 patients with HF with preserved ejection fraction (HFpEF) and obesity. Besides meeting that primary endpoint of a reduction in HF outcomes tirzepatide improved patients' HF symptoms and physical limitations versus placebo, the trial's other primary endpoint. For that endpoint, investigators used the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score.

All key secondary endpoints were also met, including improvement in exercise capacity as measured by the 6-Minute Walk-Test Distance (6MWD), reduction in the inflammation marker high-sensitivity C-reactive protein (hsCRP), and mean body weight reduction from baseline at 52 weeks. For the efficacy estimand, tirzepatide led to a 15.7% body weight reduction compared to 2.2% for placebo. For the treatment-regimen estimand, tirzepatide led to a 13.9% body weight reduction compared to 2.2% for placebo.

"HFpEF accounts for nearly half of all heart failure cases, and in the U.S. almost 60% of those impacted also live with obesity. Despite a continuing increase in the number of people with both HFpEF and obesity, treatment options remain limited," said Jeff Emmick, MD, PhD, senior vice president, product development, Lilly. "Previous incretin studies in this population focused on symptoms and physical limitations. In a first-of-its-kind trial, tirzepatide reduced severity of symptoms and improved heart failure outcomes in people with HFpEF and obesity."

HFpEF is a condition in which the heart's left pumping chamber becomes stiff and unable to fill properly. It is associated with a high burden of symptoms and physical limitations affecting daily life, including fatigue, shortness of breath, reduced ability to exercise and swelling of extremities.

The overall safety profile of tirzepatide in the SUMMIT trial was consistent with previously reported tirzepatide studies, including SURMOUNT and SURPASS. The most frequently reported adverse events in SUMMIT were primarily gastrointestinal in nature and generally mild to moderate in severity. The most common adverse events for patients treated with tirzepatide were diarrhea, nausea, constipation and vomiting.

Lilly will continue to evaluate the SUMMIT results, which will be presented at an upcoming medical meeting and submitted to a peer-reviewed journal. Lilly plans to submit the SUMMIT study results to the FDA and other regulatory agencies.