Eli Lilly has announced positive results from its Phase III SUMMIT trial, evaluating tirzepatide in individuals with heart failure with preserved ejection fraction (HFpEF) and obesity. The double-blind, multi-center, randomized, placebo-controlled study, which involved 731 participants across multiple countries, met both primary endpoints, demonstrating a significant reduction in heart failure outcomes risk.
The study revealed that tirzepatide led to a 38% decrease in heart failure outcomes risk compared to placebo. Furthermore, the risk of hospitalization for heart failure was reduced by 56% in the tirzepatide group. These findings highlight the potential of tirzepatide to address a critical unmet need in the treatment of HFpEF, a condition affecting millions worldwide.
Improvements in Symptoms and Physical Function
Beyond the primary endpoints, the SUMMIT trial also assessed the impact of tirzepatide on heart failure symptoms and physical limitations. Patients treated with tirzepatide experienced a nearly 25-point increase in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), compared to a 15-point improvement for those on placebo. This indicates a substantial improvement in the quality of life for patients receiving tirzepatide.
In addition, tirzepatide-treated patients showed improved exercise capacity, walking approximately 30 meters farther in six minutes than those who received placebo. These results suggest that tirzepatide can enhance physical function and reduce the burden of HFpEF on daily activities.
Weight Reduction and hsCRP Levels
The SUMMIT trial also demonstrated the beneficial effects of tirzepatide on body weight and inflammation. Patients on tirzepatide experienced an average body weight reduction of 15.7% compared to 2.2% in the placebo group. A reduced high-sensitivity C-reactive protein (hsCRP) level of 43.4% was also observed, suggesting a reduction in systemic inflammation.
Safety and Regulatory Submissions
Tirzepatide's overall safety profile in the SUMMIT trial was consistent with previous studies, with the most frequently reported adverse events being primarily gastrointestinal and mild to moderate in severity. Following these results, Eli Lilly has submitted tirzepatide for HFpEF and obesity treatment to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with plans to submit to other regulatory authorities at the end of the year.
Addressing Cardiometabolic Diseases
"Cardiometabolic diseases such as heart failure and obesity are closely linked and often coexist," said Jeff Emmick, senior vice-president of product development at Eli Lilly. "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. Currently, no treatments are available specifically for obesity-related HFpEF in the US."
