Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program

• Published in: Journal of the American College of Cardiology Vol. 84; no. 1; p. 27
• Main Authors: Petrie, Mark C, Borlaug, Barry A, Butler, Javed, Davies, Melanie J, Kitzman, Dalane W, Shah, Sanjiv J, Verma, Subodh, Jensen, Thomas Jon, Einfeldt, Mette Nygaard, Liisberg, Karoline, Perna, Eduardo, Sharma, Kavita, Ezekowitz, Justin A, Fu, Michael, Melenovský, Vojtěch, Ito, Hiroshi, Lelonek, Małgorzata, Kosiborod, Mikhail N
• Format: Journal Article
• Language: English
• Published: United States 02.07.2024
• Subjects: Aged; Double-Blind Method; Female; Glucagon-Like Peptides - therapeutic use; Heart Failure - blood; Heart Failure - drug therapy; Heart Failure - physiopathology; Humans; Male; Middle Aged; Natriuretic Peptide, Brain - blood; Obesity - blood; Obesity - complications; Obesity - drug therapy; Peptide Fragments - blood; Stroke Volume - drug effects; Stroke Volume - physiology; Treatment Outcome; heart failure with preserved ejection fraction; N-terminal pro–B-type natriuretic peptide; obesity; semaglutide
• ISSN: 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2024.04.022

The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. This study sought to determine if semaglutide 2.4 mg reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. This was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. In total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8-8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). In patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.