Phase III Tirzepatide Heart Failure Trial Reports Positive Topline Results
Eli Lilly has announced positive topline results from its Phase III SUMMIT trial evaluating tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. The trial met its primary composite endpoint, demonstrating statistically significant improvement in heart failure symptoms and exercise capacity compared to placebo.
The SUMMIT trial enrolled approximately 730 participants with HFpEF and a body mass index of 30 or above across clinical sites in the US, Europe, and Asia. Participants received tirzepatide (up to 15 mg weekly) or placebo for 52 weeks. The primary endpoint was a composite of cardiovascular death or worsening heart failure events, and change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
Topline results showed that tirzepatide-treated patients experienced a 38% reduction in the composite of cardiovascular death or worsening heart failure events compared to placebo. KCCQ-CSS improvements — a measure of heart failure symptoms, physical limitations, and quality of life — were also significantly greater in the tirzepatide group. Secondary endpoints including change in body weight, 6-minute walk distance, and C-reactive protein levels all favoured tirzepatide.
The safety profile was consistent with previous tirzepatide trials, with gastrointestinal events (nausea, diarrhoea, vomiting) as the most common adverse events. Discontinuation rates due to adverse events were higher in the tirzepatide group than placebo but were described by investigators as manageable.
These results position tirzepatide as a potential treatment for HFpEF in patients with obesity, a population with limited effective therapies. Lilly has indicated it intends to discuss the data with regulatory authorities, with a supplemental New Drug Application to the FDA expected in the second half of 2026. Full results are expected to be presented at a major cardiology congress later this year.