In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I-III (body mass index (BMI) 30.0-34.9 kg m-2, 35.0-39.9 kg m-2 and ≥40 kg m-2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (P value for treatment effects × BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511 .

Baylor Scott and White Research Institute Dallas TX and Department of Medicine University of Mississippi Jackson MS USA

Cardiology and Angiology Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Cardiovascular Department ASST Papa Giovanni XXIII Hospital Bergamo Italy

Clinical Cardiology Heart Failure and Research Max Super Specialty Hospital Saket New Delhi India

College of Health and Medicine The Australian National University Canberra ACT Australia

Department of Cardiology Herlev Gentofte Hospital University of Copenhagen Herlev Denmark

Department of Cardiology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Cardiovascular Disease Saint Luke's Mid America Heart Institute University of Missouri Kansas City School of Medicine Kansas City MO USA

Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology Wake Forest University School of Medicine Winston Salem NC USA

Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA

Department of General Internal Medicine 3 Kawasaki Medical School Okayama Japan

Department of Noninvasive Cardiology Medical University of Lodz Lodz Poland

Diabetes Research Centre University of Leicester Leicester UK

Division of Cardiac Surgery Li Ka Shing Knowledge Institute of St Michael's Hospital Unity Health Toronto University of Toronto Toronto ON Canada

Division of Cardiology Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL USA

Division of Cardiology Medical University of Graz Graz Austria

Division of Cardiovascular Sciences Faculty of Biology Medicine and Health University of Manchester Manchester UK

Hospital Clínico Universitario de Valencia INCLIVA Universidad de Valencia and CIBER Cardiovascular Valencia Spain

Institute for Clinical and Experimental Medicine IKEM Prague Czech Republic

Instituto de Cardiologia J F Cabral Corrientes Argentina

NIHR Leicester Biomedical Research Centre Leicester UK

Novo Nordisk A S Søborg Denmark

School of Cardiovascular and Metabolic Health University of Glasgow Glasgow UK

Section of Cardiology Department of Medicine Sahlgrenska University Hospital Ostra Gothenburg Sweden

University of Alberta Edmonton AB Canada

Nat Cardiovasc Res. 2023 Oct;2(10):858. doi: 10.1038/s44161-023-00353-4. PubMed

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Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial

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ClinicalTrials.gov
NCT04788511