By Don Tracy, Associate Editor

Data from the SUMMIT clinical trial demonstrated that tirzepatide lowered the risk of negative heart failure outcomes and enhanced symptoms and physical limitations when tested with three different doses.
Results from the SUMMIT Phase III clinical trial found that Eli Lilly’s tirzepatide, tested at doses of 5 mg, 10 mg, and 15 mg, showed statistically significant improvements in reducing heart failure with preserved ejection fraction (HFpEF) and obesity, as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), compared to placebo. According to the company, tirzepatide also demonstrated improved exercise capacity as measured by the 6-Minute Walk-Test Distance (6MWD), reduction in the inflammation marker high-sensitivity C-reactive protein (hsCRP), and a noteworthy mean body weight reduction at 52 weeks.1
"HFpEF accounts for nearly half of all heart failure cases, and in the U.S. almost 60% of those impacted also live with obesity.1,2 Despite a continuing increase in the number of people with both HFpEF and obesity, treatment options remain limited,1" said Jeff Emmick, MD, PhD, SVP, product development, Lilly, in a press release. "Previous incretin studies in this population focused on symptoms and physical limitations. In a first-of-its-kind trial, tirzepatide reduced severity of symptoms and improved heart failure outcomes in people with HFpEF and obesity."
The multi-center, randomized, double-blind, parallel, placebo-controlled SUMMIT study compared the efficacy and safety of tirzepatide to placebo in adults with HFpEF and obesity, with or without type 2 diabetes. The study included 731 patients randomly assigned in a 1:1 ratio throughout the United States, Russia, Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, and Taiwan to receive tirzepatide maximum tolerated dose (MTD) 5 mg, 10 mg, 15 mg, or placebo. The primary objectives of the study were to reduce the risk of the composite endpoint of time-to-first occurrence of urgent heart failure visit, heart failure hospitalization, oral diuretic intensification, and cardiovascular death to study completion from baseline to week 52.
Results found that tirzepatide led to a 15.7% body weight reduction compared to 2.2% for placebo in the efficacy estimand. In the treatment-regimen estimand, tirzepatide led to a 13.9% body weight reduction compared to 2.2% for placebo.
The study’s safety profile of tirzepatide was reported to be consistent with previous studies, such as SURMOUNT and SURPASS. Common adverse events included diarrhea, nausea, constipation, and vomiting, all considered mild to moderate in severity.1
According to the Heart Failure Society of America, an estimated 6.5 million Americans over the age of 20 years have heart failure, further estimating that there are 960,000 new heart failure cases annually. Additionally, it accounts for 8.5% of all heart disease deaths in the United States and could possibly account for 36% of all cardiovascular disease deaths. The risk for heart failure increases significantly after a patient reaches the age of 65 years.2
The Centers for Disease Control and Prevention state that heart failure is the leading cause of death in people over the age of 45 years. However, the trend appears to have slightly decreased in recent years. Further statistics found that from 2009-2019, men were more likely to report having heart disease than women, with the highest prevalence in adults over the age of 75 years.3
Moving forward, Lilly is expected to continue its evaluation of the SUMMIT results. At an upcoming medical meeting, the company plans on discussing the full results, with the intention of submitting the results to the FDA and other regulatory bodies later this year.1