Eli Lilly and Company announced detailed results from the SUMMIT Phase 3 trial, revealing that tirzepatide significantly reduced the risk of worsening heart failure events in adults with heart failure with preserved ejection fraction (HFpEF) and obesity. The study, presented at the American Heart Association (AHA) Scientific Sessions 2024 and published in The New England Journal of Medicine, marks a significant advancement in treating this complex condition.
The trial met both primary endpoints, demonstrating a 38% reduction in the risk of heart failure outcomes, assessed as a composite endpoint (Hazard Ratio=0.62; 95% CI 0.41 to 0.95; P=0.026), compared to placebo. Furthermore, the risk of hospitalization for heart failure was reduced by 56% in patients treated with tirzepatide.
Improvements in Symptoms and Physical Function
Patients treated with tirzepatide also experienced significant improvements in heart failure symptoms and physical limitations. The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), which measures these aspects, improved by nearly 25 points in the tirzepatide group compared to a 15-point improvement in the placebo group (Estimated median difference at 52 weeks: 6.9; 95% CI 3.3 to 10.6; P<0.001).
Secondary Endpoint Results
All key secondary endpoints were also met. Patients on tirzepatide demonstrated improved exercise capacity, walking approximately 30 meters farther in six minutes than those on placebo (38.2 meters vs. 7.9 meters). Additionally, patients treated with tirzepatide saw an average reduction in body weight of 15.7%, compared to 2.2% in the placebo group. Tirzepatide also significantly decreased high-sensitivity C-reactive protein (hsCRP), a key marker of systemic inflammation, by 43.4%, while the placebo group saw a 3.5% decrease.
Expert Commentary
"Many studies point to obesity as a major contributor to the development and severity of heart failure with a preserved ejection fraction through its effects to promote systemic and myocardial inflammation," said Milton Packer, M.D., distinguished scholar in cardiovascular science at Baylor University Medical Center at Dallas and visiting professor at Imperial College, London (steering committee chair). "The SUMMIT trial provides important insights as to how healthcare providers could have a meaningful impact on the clinical course and quality of life of patients with HFpEF and obesity."
Tirzepatide's Potential Impact
"Cardiometabolic diseases, such as heart failure and obesity, are closely linked and often coexist. New approaches are needed to address the interrelated nature of these diseases," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Currently, no treatments are available specifically for obesity-related HFpEF in the U.S. The SUMMIT data suggest that, if approved, tirzepatide could provide a significant advancement for these patients, potentially setting a new standard of care."
Safety Profile
The overall safety profile of tirzepatide in the SUMMIT trial was consistent with previously reported tirzepatide studies. The most frequently reported adverse events were primarily gastrointestinal related and generally mild to moderate in severity, including diarrhea (18.4% vs. 6.3%), nausea (17.0% vs. 6.5%) and constipation (14.8% vs. 6.0%).
Regulatory Submissions
Lilly has submitted tirzepatide for the treatment of HFpEF and obesity to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and plans to submit to other regulatory agencies starting later this year.
