Eli Lilly and Company (NYSE: LLY) announced detailed results from the SUMMIT Phase 3 trial showing tirzepatide significantly reduced the risk of worsening heart failure events in adults with heart failure with preserved ejection fraction (HFpEF) and obesity. Patients treated with tirzepatide also experienced notable improvements in heart failure symptoms and physical limitations. The results were published in The New England Journal of Medicine simultaneously with a presentation at the American Heart Association (AHA) Scientific Sessions 2024.

Both primary endpoints were met. Tirzepatide showed a 38% reduction in the risk of heart failure outcomes, assessed as a composite endpoint, compared to placebo. Risk of hospitalization for heart failure was reduced by 56%. In addition, patients taking tirzepatide saw a nearly 25-point improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS),¹ which measures symptoms and physical limitations associated with heart failure, compared to a 15-point improvement for the placebo group.² 

"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." 

All key secondary endpoints were also met, with patients treated with tirzepatide demonstrating improved exercise capacity, walking approximately 30 meters farther in six minutes than those on placebo (38.2 meters vs. 7.9 meters).² Additionally, patients treated with tirzepatide saw an average reduction in body weight of 15.7%, compared to 2.2% in the placebo group.² 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.

"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. At Lilly, we want to better understand the root causes of these conditions and how they impact each other so we're better able to treat them," 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."

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. The most common adverse events reported by those on tirzepatide compared with placebo, respectively, were diarrhea (18.4% vs. 6.3%), nausea (17.0% vs. 6.5%) and constipation (14.8% vs. 6.0%). Adverse events led to discontinuation of study treatment in 23 participants taking tirzepatide and five taking placebo. 

Additional data from SUMMIT will be presented during AHA and published in peer-reviewed journals. Lilly 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.