SUMMIT Meets Primary Endpoint for Safety, Efficacy of Tirzepatide: Topline Results

Patients who have heart failure with preserved ejection fraction (HFpEF) and obesity can be safely and effectively treated with tirzepatide (Mounjaro and Zepbound; Eli Lilly) through 2 years of follow-up, with topline data from the phase III SUMMIT trial showing the drug reduces heart failure events and improves other patient-centered outcomes compared with placebo.

Tirzepatide, like semaglutide (Wegovy and Ozempic; Novo Nordisk), is part of the new class of injectable glucagon-like peptide-1 (GLP-1) receptor agonists; unlike semaglutide, it also activates the hormone glucose-dependent insulinotropic polypeptide (GIP).

The SUMMIT trial, the drug’s manufacturer announced today, met statistical significance for both of its primary endpoints. Tirzepatide reduced a composite of heart failure outcomes that included time to first occurrence of urgent HF visit, HF hospitalization, oral diuretic intensification, and CV death (HR 0.62; 95% CI 0.41-0.95) at a median follow-up period of 104 weeks compared with placebo, and it improved heart failure symptoms and physical limitations as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at the 1-year mark.

The KCCQ-CSS improved by 24.8 points for those randomized to tirzepatide (5, 10, or 15 mg) and by 15 points in the placebo arm.

The trial, which included 731 patients with or without diabetes from US, Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, Russia, and Taiwan, also met all key secondary endpoints, including longer 6-minute walk-test distance, lower level of high-sensitivity C-reactive protein, and reduced body weight through 1 year. The researchers estimated that while the placebo group only lost 2.2% body weight over the course of the study, the study group lost 15.7%.

Patients in SUMMIT most frequently reported adverse events related to gastrointestinal symptoms, including diarrhea, nausea, constipation, and vomiting, and these were mostly deemed mild to moderate in severity.

Today’s announcement falls on the heels of data suggesting tirzepatide might lead to increased weight loss compared with semaglutide, although other research has shown this effect can be quickly reversed if the drug is stopped. 

Eli Lilly plans to present the full SUMMIT dataset at an upcoming medical meeting and publish the details in a peer-reviewed journal before submitting them to the US Food and Drug Administration later in the year.