Poster Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

Once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes: main results from the STEP-HFpEF DM trial (#266)

Andrew Sindone 1 2 3 , Mikhail Kosiborod 4 , Mark C Petrie 5 , Barry A Borlaug 6 , Javed Butler 7 8 , Melanie J Davies 9 10 , G. Kees Hovingh 11 12 , Dalane W Kitzman 13 , Daniél Vega Møller 11 , Marianne Bach Treppendahl 11 , Subodh Verma 14 , Thomas J Jensen 11 , Karoline Liisberg 11 , Marie L Lindegaard 11 , Sanjiv J Shah 15
  1. Department of Cardiology, Concord Repatriation General Hospital, Sydney, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia
  3. Ryde Hospital, Eastwood, Sydney, NSW, Australia
  4. Department of Cardiovascular Disease, Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA
  5. School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
  6. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
  7. Baylor Scott and White Research Institute, Dallas, TX, USA
  8. Department of Medicine, University of Mississippi, Jackson, MS, USA
  9. Diabetes Research Centre, University of Leicester, Leicester, UK
  10. NIHR Leicester Biomedical Research Centre, Leicester, UK
  11. Novo Nordisk A/S, Søborg, Denmark
  12. The Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
  13. Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA
  14. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
  15. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Background and Aims: Obesity and type 2 diabetes (T2D) are highly prevalent in people who have heart failure (HF) with preserved ejection fraction (HFpEF) and are associated with an especially high burden of symptoms and functional impairment. No approved therapies specifically target obesity-related HFpEF in patients with T2D. The STEP-HFpEF DM randomised controlled trial (NCT04916470) tested the efficacy and safety of semaglutide 2.4 mg compared with placebo in patients with obesity-related HFpEF and T2D.

Methods: In this double-blind trial, we randomised 616 patients across 108 sites in 16 countries with HFpEF, a body mass index (BMI) of ≥30 kg/m2 and T2D to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and body weight. Confirmatory secondary endpoints were change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, and change in KCCQ-CSS and 6MWD) and change in C-reactive protein. Exploratory endpoints included NTproBNP and adjudicated HF events.

Results: Median age was 69 years, 44% were women, median BMI was 36.9 kg/m2, KCCQ-CSS was 59.4 points, 6MWD was 280 meters, N-terminal pro B-type natriuretic peptide was 493 pg/mL, left ventricular ejection fraction was 56%, and 29.4% were in New York Heart Association functional (NYHA) class II–IV. Most patients were treated with diuretics (80.8%); 32.5% received mineralocorticoid receptor antagonists and 32.8% received sodium–glucose co‐transporter-2 inhibitors.

Conclusion: STEP-HFpEF DM randomised patients with obesity-related HFpEF and T2D who have marked symptomatic and functional impairment, and will determine whether semaglutide can improve symptoms, physical limitations and exercise function in this group with a large need for additional therapies.