Finding a Role for GLP-1 RAs, Incretin Therapies in Heart Failure, with Muthiah Vaduganathan, MD, MPH

GLP-1 receptor agonists and combination incretin therapies have taken the medical community by storm in recent years with trial after trial proving benefits on outcomes across a multitude of diseases, including weight management, secondary prevention of cardiovascular disease, and, now, obesity-related heart failure with preserved ejection fraction (HFpEF) based on data from the SUMMIT trial.

A multicenter, randomized, double-blind, parallel, placebo-controlled phase 3 trial, SUMMIT assessed the safety and efficacy of tirzepatide among a cohort of 731 adult patient adults with HFpEF and obesity, with or without type 2 diabetes, enrolled at sites in 10 countries across 4 continents. The trial leveraged a pair of primary outcomes of interest—a composite of time-to-first occurrence of urgent heart failure visit, heart failure hospitalization, oral diuretic intensification and cardiovascular death to study completion and the change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to week 52.¹

Results of the trial suggested a composite endpoint event occurred among 9.9% of the tirzepatide group and 15.3% of the placebo group (HR, 0.62; 95% CI, 0.41 to 0.95; P = .026). Analysis of KCCQ-CSS at 52 weeks suggested use of tirzepatide was associated with a mean change of 19.5 (SD, 1.2) from baseline to week 52 compared to a change of 12.7 (SD, 1.3) among the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P <.001).¹

Although not examining hospitalization outcomes, SUMMIT is the second trial to demonstrate meaningful changes in quality of life among patients with obesity-related HFpEF, with the STEP-HFpEF program finding benefit on KCCQ with use of semaglutide.²

At the American Heart Association (AHA) Annual Scientific Sessions 2024, Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science of Brigham and Women’s Hospital, took part in a debate session where he argued in favor of a role for GLP-1 receptor agonists in heart failure care. As part of our on-site coverage of AHA 24, we sat down with Vaduganathan to learn more about how he envisions GLP-1 receptor agonists and incretin therapies fitting into heart failure care in light of recent data.

Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others.

References:

1. Packer M. Tirzepatide for Patients with Heart Failure with Preserved Ejection Fraction and Obesity: the SUMMIT Trial. Paper presented at: American Heart Association Scientific Sessions 2024; November 15 - 18; Chicago, Il. Accessed November 16, 2024.
2. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963