Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial

  • Nat Med. 2024 Jul;30(7):2049-2057. doi: 10.1038/s41591-024-02996-7.
Donna H Ryan  1 ,  Ildiko Lingvay  2 ,  John Deanfield  3 ,  Steven E Kahn  4 ,  Eric Barros  5 ,  Bartolome Burguera  6 ,  Helen M Colhoun  7 ,  Cintia Cercato  8 ,  Dror Dicker  9 ,  Deborah B Horn  10 ,  G Kees Hovingh  5 ,  Ole Kleist Jeppesen  5 ,  Alexander Kokkinos  11 ,  A Michael Lincoff  12 ,  Sebastian M Meyhöfer  13 ,  Tugce Kalayci Oral  5 ,  Jorge Plutzky  14 ,  André P van Beek  15 ,  John P H Wilding  16 ,  Robert F Kushner  17
Affiliations
  • 1. Pennington Biomedical Research Center, Baton Rouge, LA, USA. [email protected].
  • 2. Department of Internal Medicine/Endocrinology and Peter O' Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 3. Institute of Cardiovascular Science, University College London, London, UK.
  • 4. VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
  • 5. Novo Nordisk A/S, Søborg, Denmark.
  • 6. Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA.
  • 7. Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
  • 8. Obesity Unit, Department of Endocrinology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.
  • 9. Internal Medicine Department D, Hasharon Hospital-Rabin Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 10. Center for Obesity Medicine and Metabolic Performance, Department of Surgery, University of Texas McGovern Medical School, Houston, TX, USA.
  • 11. First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
  • 12. Department of Cardiovascular Medicine, Cleveland Clinic, and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
  • 13. Institute of Endocrinology & Diabetes, University of Lübeck, Lübeck, Germany.
  • 14. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • 15. University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, the Netherlands.
  • 16. Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK.
  • 17. Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
PMID: 38740993 DOI: 10.1038/s41591-024-02996-7
Abstract

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting Cardiovascular Disease, overweight or Obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .