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

Semaglutide and cardiovascular outcomes in patients with overweight or obesity who do not have diabetes (#242)

Melissa Leung 1 2 , Abraham M Lincoff 3 , Kirstine Brown-Frandsen 4 , Helen M Colhoun 5 , John Deanfield 6 , Scott S Emerson 7 , Sille Esbjerg 4 , Søren Hardt-Lindberg 4 , G. Kees Hovingh 4 8 , Steven E Kahn 9 10 , Robert F Kushner 11 , Ildiko Lingvay 12 , Tugce K Oral 4 , Marie M Michelsen 4 , Jorge Plutzky 13 , Christoffer W Tornøe 4 , Donna H Ryan 14
  1. Liverpool Hospital, Liverpool, Sydney, NSW, Australia
  2. School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia
  3. Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
  4. Novo Nordisk A/S , Søborg, Denmark
  5. Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK
  6. Institute of Cardiovascular Sciences, University College London, London, UK
  7. Department of Biostatistics, University of Washington, Seattle, WA, USA
  8. The Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
  9. Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, USA
  10. Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA
  11. The Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
  12. Department of Internal Medicine/Endocrinology and Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
  13. Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
  14. Pennington Biomedical Research Center, Baton Rouge, LA, USA

Background: Semaglutide, a long-acting agonist of the glucagon-like peptide-1 receptor, is approved in people with type 2 diabetes with overweight or obesity. It has been shown to reduce the risk of adverse cardiac events in people with type 2 diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.

Methods: In a multicentre, randomised, double-blind, placebo-controlled, event-driven superiority trial, we enrolled 17,604 patients aged 45 years or older with pre-existing cardiovascular disease and a body mass index of ≥27 kg/m2 who did not have diabetes. Patients were randomly assigned to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo. The primary cardiovascular efficacy endpoint was any component of the composite of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke in a time-to-first-event analysis. Confirmatory secondary endpoints, assessed in a time-to-first-event analyses and tested in hierarchical order, were death from cardiovascular causes, a heart failure composite of death from cardiovascular causes or hospitalisation or urgent medical visit for heart failure, and death from any cause. Supportive secondary endpoints, also assessed in a time-to-first-event analyses but without control for multiplicity, included expanded cardiovascular composite endpoints, individual components of cardiovascular composite endpoints, a composite nephropathy endpoint, progression to diabetes or progression to prediabetes as diagnosed by glycated haemoglobin levels. Changes from randomisation to week 104 in body weight, glycated haemoglobin concentrations and other cardiovascular risk factors were measured.

Results: The trial met its primary objective, with a 20% reduction in the primary endpoint with semaglutide compared with placebo. Details of primary and secondary efficacy endpoints, and safety findings, will be presented.

Conclusions: In patients with pre-existing cardiovascular disease and overweight or obesity, but without diabetes, weekly subcutaneous semaglutide 2.4 mg was superior to placebo in reducing the incidence of major adverse cardiovascular events.