Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes

Mikhail N Kosiborod1, Mark C Petrie1, 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.); the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (M.C.P.), the Diabetes Research Centre, University of Leicester, and the NIHR Leicester Biomedical Research Centre, Leicester (M.J.D.), and the Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester (F.Z.A.) - all in the United Kingdom; the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (B.A.B.); the Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Novo Nordisk, Søborg (G.K.H., D.V.M., M.B.T., T.J.J., K.L., M.L.L.), and the Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev (M. Schou) - both in Denmark; 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 Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto (S.V.), and the University of Alberta, Edmonton (J.A.E.) - both in Canada; the College of Health and Medicine, Australian National University, Canberra, ACT, Australia (W.A.); the Heart Failure Unit, Cardiology Department, Rabin Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (T.B.-G.); Max Super Speciality Hospital, Saket, New Delhi, India (V.C.); the Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Östra, 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 - both in Valencia, Spain (J.N.); Instituto de Cardiologia J.F. Cabral, Corrientes, Argentina (E.P.); ASST (Azienda Socio Sanitaria Territoriale) Papa Giovanni XXIII, Bergamo, Italy (M. Senni); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore (K.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); the Medical University of Graz, Graz, Austria (D.V.L.); Cardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (D.W.); and the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.).

Insights

Semaglutide significantly improved symptoms and reduced weight in patients with obesity, type 2 diabetes, and heart failure with preserved ejection fraction. This offers a new therapeutic option for this complex patient population.

Area of Science:

  • Cardiology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Obesity and type 2 diabetes are common in heart failure with preserved ejection fraction (HFpEF), increasing symptom burden.
  • Currently, no approved therapies specifically address obesity-related HFpEF in patients with type 2 diabetes.

Purpose of the Study:

  • To evaluate the efficacy of semaglutide in patients with HFpEF, obesity, and type 2 diabetes.
  • To assess the impact of semaglutide on HFpEF symptoms, body weight, and other relevant clinical outcomes.

Main Methods:

  • A 52-week randomized trial assigned 616 patients with HFpEF, BMI ≥30, and type 2 diabetes to receive weekly semaglutide (2.4 mg) or placebo.
  • Primary endpoints included changes in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and body weight.
  • Secondary endpoints included changes in 6-minute walk distance, a composite of major adverse cardiovascular events, and C-reactive protein (CRP) levels.

Main Results:

  • Semaglutide significantly improved KCCQ-CSS (13.7 vs 6.4 points) and reduced body weight (-9.8% vs -3.4%) compared to placebo.
  • Improvements were also observed in 6-minute walk distance, a hierarchical composite endpoint, and CRP levels, favoring semaglutide.
  • Serious adverse events were less frequent in the semaglutide group (17.7%) than in the placebo group (28.8%).

Conclusions:

  • Semaglutide demonstrated significant benefits in reducing symptoms and physical limitations associated with HFpEF in patients with obesity and type 2 diabetes.
  • Greater weight loss was achieved with semaglutide compared to placebo over 52 weeks.
  • Semaglutide represents a promising therapeutic option for managing obesity-related HFpEF in patients with type 2 diabetes.
Abstract

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