Semaglutide and NT-proBNP in Obesity-Related HFpEF
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BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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The median NT-proBNP in SUMMIT was significantly lower than in the STEP-HFpEF program (median ≈470 pg/mL) and substantially lower than in other large-scale outcome trials in HFpEF (median 900-1400 pg/mL).
“This level was significantly lower than that in the STEP-HFpEF program (median, ≈470 pg/mL)36 and substantially lower than in other large-scale outcome trials in HFpEF (median 900–1400 pg/mL).3–6”
From Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity (2025) · cites this paper as [36]
The magnitude of the decline in NT-proBNP in SUMMIT was less marked than the 18% decrease observed in the STEP-HFpEF trials, potentially because of lower baseline value and smaller decrease in body weight with semaglutide compared with tirzepatide.
“The magnitude of the decline in NT-proBNP was less marked than the 18% decrease observed in the STEP-HFpEF trials,36 potentially because of our much lower baseline value and because of the smaller decrease in body weight produced by semaglutide (ie, ≈8%–9%) compared with tirzepatide.”
From Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity (2025) · cites this paper as [36]
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- Authors
- Petrie, M. C., Borlaug, B. A., Butler, J., Davies, M. J., Kitzman, D. W., Shah, S. J., Verma, S., Jensen, T. J., Einfeldt, M. N., Liisberg, K., Perna, E., Sharma, K., Ezekowitz, J. A., Fu, M., Melenovský, V., Ito, H., Lelonek, M., & Kosiborod, M. N.
- Affiliations
- University of Glasgow (GB)
- Mayo Clinic (US)
- University of Mississippi Medical Center (US)
- University of Leicester (GB)
- Wake Forest University Health Sciences (US)
- Northwestern University (US)
- St. Michael's Hospital (CA)
- Novo Nordisk (Denmark) (DK)
- Johns Hopkins University (US)
- University of Alberta (CA)
- Sahlgrenska University Hospital (SE)
- Institute of Clinical and Experimental Medicine (CZ)
- Kawasaki Medical School (JP)
- Medical University of Lodz (PL)
- Saint Luke's Hospital (US)
- Corresponding author
- Kosiborod, Mikhail N.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2024-07
- Volume
- 84
- Issue
- 1
- Pages
- 27-40
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W4396873474
- Cited by
- 95
- References
- 28
- Citations by year
- 2026: 31 · 2025: 49 · 2024: 15
- FWCI
- 28.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- semaglutide, NT-proBNP, obesity, heart failure with preserved ejection fraction, GLP-1 receptor agonists, weight loss, health status, type 2 diabetes, natriuretic peptides, obesity cardiomyopathy, Kansas City Cardiomyopathy Questionnaire, mechanical unloading, pathobiology
- MeSH terms
- Semaglutide, Aged, Double-Blind Method, Glucagon-Like Peptides, Female, Heart Failure, Humans, Male, Middle Aged, Obesity, Peptide Fragments, Stroke Volume, Treatment Outcome, Natriuretic Peptide, Brain
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