Tirzepatide Reduces Heart Failure Outcomes in Obesity-Related Heart Failure

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Eli Lilly and Company have announced positive topline data from their phase 3 SUMMIT trial evaluating use of tirzepatide in adults with heart failure.

A phase 3 trial assessing use of tirzepatide injection 5mg, 10 mg, or 15 mg in adults with heart failure with preserved ejection fraction (HFpEF) and obesity, results of the study indicate use of the dual GIP/GLP-1 receptor agonist was associated with statistically significant improvements in both primary endpoints, with benefit seen on risk of heart failure outcomes as well as heart failure symptoms and physical limitations. According to the August 1, 2024 announcement, tirzepatide use was associated with a 38% relative risk reduction in time-to-first occurrence of heart failure outcomes relative to placebo therapy over 104 weeks of follow-up.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. Despite a continuing increase in the number of people with both HFpEF and obesity, treatment options remain limited," said Jeff Emmick, MD, PhD, senior vice president, product development at Eli Lily and Company.¹ "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 first dual GIP/GLP-1 receptor agonist to score US Food and Drug Administration (FDA) approvals for type 2 diabetes and obesity, tirzepatide has kept pace with the general fervor surrounding incretin therapies, driven primarily by semaglutide in recent years as a result of its therapeutic promise. As the community has witnessed the role of GLP-1 receptor agonists grow, excitement and anticipation surrounding trial results for dual and triple incretin therapies has grown in tandem.²

The announcement related to use in HFpEF comes less than a year after semaglutide and Novo Nordisk debuted their STEP-HFpEF program, which included 2 trials examining use of semaglutide against placebo for symptom scores and functional outcomes. Unlike these trials, the phase SUMMIT study included heart failure outcomes as a primary endpoint.^1,3

A multicenter, randomized, double-blind, parallel, placebo-controlled phase 3 trial, SUMMIT was designed to compare the safety and efficacy of tirzepatide against placebo therapy in adults with HFpEF and obesity, with or without type 2 diabetes. Conducted in 10 countries across 4 continents, the study randomized 731 patients in a 1:1 ratio and leveraged 2 primary endpoints. The first primary endpoint was a composite endpoint of time-to-first occurrence of urgent heart failure visit, heart failure hospitalization, oral diuretic intensification and cardiovascular death to study completion and the second primary endpoint was change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to week 52.¹

Results indicated tirzepatide demonstrated statistically significant improvements relative to placebo therapy for both the composite endpoint of heart failure outcomes (HR, 0.62; 95% CI, 0.41 to 0.95; P = .026) and in mean change from baseline of KCCQ-CSS (24.8 vs 15.0). The trial also included multiple secondary endpoints and Eli Lilly and Company highlighted results from some of these within their release. Specifically, the company called attention to improvement in exercise capacity as measured by the 6-Minute Walk-Test Distance, reduction in hsCRP, and mean body weight reduction from baseline at 52 weeks. When assessing body weight changes, the efficacy estimated indicated patients receiving tirzepatide experienced a mean reduction in body weight of 15.7% vs 2.2% for placebo.¹

According to the announcement, Eli Lilly and Company plans to submit the SUMMIT study results to the FDA and other regulatory agencies later in 2024.¹

References:

1. Eli Lilly and Company. Lilly’s tirzepatide successful in phase 3 study showing benefit in adults with heart failure with preserved ejection fraction and obesity. Eli Lilly and Company. August 1, 2024. Accessed August 1, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-successful-phase-3-study-showing-benefit.
2. Campbell P. FDA approves Tirzepatide (Zepbound) for Chronic Weight Management. HCP Live. November 8, 2023. Accessed August 1, 2024. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management.
3. Campbell P. Step HFPEF DM: Semaglutide 2.4 mg improves functional status, symptoms in patients with diabetes, HFPEF. HCP Live. April 6, 2024. Accessed August 1, 2024. https://www.hcplive.com/view/step-hfpef-dm-semaglutide-2-4-mg-improves-functional-status-symptoms-in-patients-with-diabetes-hfpef.