Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial
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Background People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate 2 , kidney replacement therapy, and kidney or CV death) by 24%. Objectives This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. Methods Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. Results A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV d…
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In a randomized placebo-controlled trial of semaglutide in people with type 2 diabetes and CKD, semaglutide significantly reduced the risk of heart failure.
“In addition, heart failure was a prespecified outcome of the randomized, placebo-controlled trial of semaglutide in people with type 2 diabetes and CKD and found a significant reduction in the risk of heart failure among those randomized to active semaglutide (284).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [284]
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- Authors
- Pratley, R. E., Tuttle, K. R., Rossing, P., Rasmussen, S., Perkovic, V., Nielsen, O. W., Mann, J. F. E., MacIsaac, R. J., Kosiborod, M. N., Kamenov, Z., Idorn, T., Hansen, M. B., Hadjadj, S., Bakris, G., Baeres, F. M. M., & Mahaffey, K. W.
- Affiliations
- AdventHealth Orlando (US)
- University of Washington (US)
- University of Copenhagen (DK)
- Novo Nordisk (Denmark) (DK)
- UNSW Sydney (AU)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- The University of Melbourne (AU)
- Saint Luke's Hospital (US)
- Alexandrovska Hospital (BG)
- Centre National de la Recherche Scientifique (FR)
- American Heart Association (US)
- Stanford Medicine (US)
- Corresponding author
- Pratley, Richard E.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2024-10
- Volume
- 84
- Issue
- 17
- Pages
- 1615-1628
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W4402066342
- Cited by
- 132
- References
- 28
- Citations by year
- 2026: 55 · 2025: 67 · 2024: 10
- FWCI
- 43.47
- 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)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- HAL (submittedVersion, cc-by-nc-nd)
- Funders
- European Commission
- Novo Nordisk A/S
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- semaglutide, heart failure, type 2 diabetes, chronic kidney disease, cardiovascular mortality, GLP-1 receptor agonists, FLOW trial, NYHA functional class, heart failure with reduced ejection fraction, renal replacement therapy, heart failure hospitalization, diuretic therapy, cardiovascular risk reduction, SGLT2 inhibitors
- MeSH terms
- Semaglutide, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Female, Heart Failure, Humans, Hypoglycemic Agents, Male, Middle Aged, Treatment Outcome, Renal Insufficiency, Chronic
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