Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity

Mikhail N Kosiborod1, Steen Z Abildstrøm1, Barry A Borlaug1

  • 1From the Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City (M.N.K.); Novo Nordisk, Søborg (S.Z.A., S.R., G.K.H., M.L.L., D.V.M., M.B.T.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Diabetes Research Centre, University of Leicester, and National Institute for Health and Care Research Leicester Biomedical Research Centre (M.D.), Leicester, the Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester (F.Z.A.), and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.) - all in the United Kingdom; the Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC (D.W.K.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); the Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and University of Alberta, Edmonton (J.E.) - both in Canada; the College of Health and Medicine, the Australian National University, Canberra, ACT, Australia (W.A.); Max Super Specialty Hospital, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden (M.F.); the Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan (H.I.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); the Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER (Centro de Investigación Biomédica en Red) Cardiovascular, Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Sociosanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); John Hopkins Hospital, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.V.M.); Medical University of Graz, Graz, Austria (D.L.); and Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.).

Insights

Semaglutide significantly improved symptoms and exercise function in patients with obesity-related heart failure with preserved ejection fraction. This obesity treatment also led to substantial weight loss and reduced inflammation.

Area of Science:

  • Cardiology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Heart failure with preserved ejection fraction (HFpEF) prevalence is rising, particularly in obese individuals.
  • Obesity-related HFpEF presents significant symptom burden and functional limitations.
  • Current therapeutic options for obesity-related HFpEF are limited.

Purpose of the Study:

  • To evaluate the efficacy of semaglutide in treating heart failure with preserved ejection fraction in patients with obesity.
  • To assess the impact of semaglutide on symptoms, physical limitations, exercise function, and body weight.

Main Methods:

  • A randomized trial involving 529 patients with HFpEF and body-mass index ≥30.
  • Participants received once-weekly semaglutide (2.4 mg) or placebo for 52 weeks.
  • Primary endpoints included changes in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and body weight.

Main Results:

  • Semaglutide significantly improved KCCQ-CSS scores (16.6 vs 8.7 points) and reduced body weight (-13.3% vs -2.6%).
  • Exercise function, measured by 6-minute walk distance, improved significantly with semaglutide (+21.5 m vs +1.2 m).
  • Semaglutide also reduced C-reactive protein levels, indicating decreased inflammation, and had a better safety profile regarding serious adverse events.

Conclusions:

  • Semaglutide at 2.4 mg demonstrated significant benefits in reducing symptoms and physical limitations in patients with HFpEF and obesity.
  • The treatment resulted in greater weight loss and improved exercise capacity compared to placebo.
  • Semaglutide represents a promising therapeutic approach for managing obesity-related HFpEF.
Abstract

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