Lilly's tirzepatide cuts HFpEF heart failure risk by 38% in obese adults

In a groundbreaking study, the drug tirzepatide has shown promising results in alleviating symptoms of heart failure and physical limitations in patients. The study, conducted by Eli Lilly and Company, demonstrated significant improvements in exercise capacity, weight loss, and reduced systemic inflammation in patients receiving the medication. This is the first trial of its kind to assess the impact of tirzepatide on these factors in adults with heart failure and preserved ejection fraction (HFpEF) and obesity.

The SUMMIT Phase 3 trial revealed that tirzepatide significantly reduced the risk of worsening heart failure events in adults with HFpEF and obesity. Detailed results indicate that patients treated with tirzepatide experienced notable improvements in heart failure symptoms and physical limitations. The findings were published in The New England Journal of Medicine and presented at the American Heart Association (AHA) Scientific Sessions 2024.

The study met both primary endpoints, with tirzepatide demonstrating a 38% reduction in the risk of heart failure outcomes compared to placebo. Additionally, the risk of hospitalization for heart failure was reduced by 56%. Patients taking tirzepatide also saw a nearly 25-point improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), compared to a 15-point improvement in the placebo group. This questionnaire measures symptoms and physical limitations associated with heart failure.

Dr. Milton Packer, distinguished scholar in cardiovascular science at Baylor University Medical Center at Dallas and visiting professor at Imperial College, London, highlighted the significance of the findings. He noted that the SUMMIT trial provides valuable insights into how healthcare providers can positively impact the clinical course and quality of life for patients with HFpEF and obesity.

All key secondary endpoints were also achieved, with patients treated with tirzepatide showing improved exercise capacity and walking approximately 30 meters farther in six minutes than those on placebo. Additionally, patients treated with tirzepatide experienced an average reduction in body weight of 15.7%, compared to 2.2% in the placebo group. Tirzepatide also significantly reduced high-sensitivity C-reactive protein (hsCRP), a key marker of systemic inflammation, by 43.4%, while the placebo group saw a 3.5% decrease.

Dr. Jeff Emmick, senior vice president of product development at Lilly, emphasized the importance of understanding the interrelated nature of cardiometabolic diseases, including heart failure and obesity. He noted that new approaches are needed to address these conditions, and the SUMMIT data suggest that tirzepatide could provide significant advancements for patients if approved, potentially setting a new standard of care.

The overall safety profile of tirzepatide in the SUMMIT trial was consistent with previous studies. The most frequently reported adverse events were gastrointestinal-related and generally mild to moderate in severity. Common adverse events reported by those on tirzepatide included diarrhea, nausea, and constipation. Adverse events led to discontinuation of the study treatment in some participants.

Lilly has initiated submissions for 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 later this year. Additional data from the SUMMIT trial will be presented during the AHA conference and published in peer-reviewed journals.

SUMMIT was a multi-center, randomized, double-blind, placebo-controlled Phase 3 study comparing the efficacy and safety of tirzepatide to placebo in adults with HFpEF and obesity. The trial involved 731 participants from various countries, including the U.S., Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, Russia, and Taiwan. The primary objectives were to reduce the risk of heart failure outcomes and demonstrate improvements in heart failure symptoms and physical limitations over 52 weeks.

Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. It activates the body's receptors for GIP and GLP-1, which are natural incretin hormones found in areas of the brain important for appetite regulation. Tirzepatide decreases calorie intake by affecting appetite and has been approved for treating type 2 diabetes and obesity.

Overall, the SUMMIT trial's positive results highlight the potential of tirzepatide to significantly improve the lives of patients with HFpEF and obesity, offering hope for better management and treatment of these conditions.