Diabetes Dialogue: STEP-HFpEF Reaction


Less than 2 weeks after the release of their SELECT reaction podcast, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, sit down for a special edition episode of Diabetes Dialogue to discuss STEP-HFpEF data and the implications for semaglutide 2.4 mg.

For endocrinologists and the diabetes care team, GLP-1 receptor agonists have been a familiar face for nearly 2 decades. In recent years, as its role has expanded into chronic weight management, healthcare professionals outside of these disciplines have begun to familiarize themselves with the class.

In August 2023, it became evident cardiology would be the next specialty to find a role for at least one member of the class, with data from the SELECT and STEP-HFpEF trials purporting significant cardiovascular benefit from use of semaglutide 2.4 mg (Wegovy) in patient populations with obesity.1,2

On August 8, 2023, Novo Nordisk announced topline data from their SELECT trial, which assessed use of once-weekly semaglutide 2.4 mg against placebo therapy on cardiovascular events in people with overweight or obesity and established cardiovascular disease. With a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke serving as the primary outcome of interest, topline data from the trial suggest use of semaglutide 2.4 mg was associated with a 20% relative risk reduction compared to placebo.1

On August 25, 2023, results of the STEP-HFpEF trial were presented at the European Society of Cardiology (ESC) Congress 2023 and simultaneously published in the New England Journal of Medicine. A randomized, double-blind, placebo-controlled trial conducted at 96 sites in Asia, Europe, and North and South America, the STEP-HFpEF trial assessed the effects of semaglutide 2.4 mg (Wegovy) against placebo therapy on symptoms and functional status among 529 adults with obesity and heart failure with preserved ejection fraction (HFpEF).2

The trial had dual primary endpoints defined as change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight at 52 weeks. Results presented at ESC Congress 2023 suggested the mean change in the KCCQ-CSS was 16.6 points with semaglutide 2.4 mg and 8.7 points with placebo (estimated treatment difference [ETD], 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; < .001). For change in body weight, results suggested the mean percentage change in body weight was −13.3% with semaglutide 2.4 mg and −2.6% with placebo (ETD, −10.7 percentage points; 95% CI, −11.9 to −9.4; < .001).2

Less than 2 weeks after the release of an episode showcasing reaction to the SELECT trial, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, sat down for another special edition episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives to share their thoughts on STEP-HFpEF results.


  1. Campbell P. Select trial shows semaglutide 2.4 mg could reduce cardiovascular risk. HCP Live. August 8, 2023. Accessed August 24, 2023. https://www.hcplive.com/view/select-trial-shows-semaglutide-2-4-mg-could-reduce-cardiovascular-risk.
  2. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. The New England Journal of Medicine. Published online August 25, 2023. doi:10.1056/NEJMoa2306963

Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

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