The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial

Benjamin M Scirica; A Michael Lincoff; Ildiko Lingvay; Pawel Bogdanski; Silvio Buscemi; Helen Colhoun; Anca-Elena Craciun; Marat Ezhov; Søren Hardt-Lindberg; Ole Kleist Jeppesen; Ana Laura S A Matos; Koichi Node; Francois Schiele; Hermann Toplak; André van Beek; Peter E Weeke; Stephen D Wiviott; John Deanfield; Donna Ryan

doi:10.1016/j.jacc.2024.08.007

The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial

J Am Coll Cardiol. 2024 Aug 27:S0735-1097(24)08156-7. doi: 10.1016/j.jacc.2024.08.007. Online ahead of print.

Authors

Benjamin M Scirica¹, A Michael Lincoff², Ildiko Lingvay³, Pawel Bogdanski⁴, Silvio Buscemi⁵, Helen Colhoun⁶, Anca-Elena Craciun⁷, Marat Ezhov⁸, Søren Hardt-Lindberg⁹, Ole Kleist Jeppesen⁹, Ana Laura S A Matos⁹, Koichi Node¹⁰, Francois Schiele¹¹, Hermann Toplak¹², André van Beek¹³, Peter E Weeke⁹, Stephen D Wiviott¹⁴, John Deanfield¹⁵, Donna Ryan¹⁶

Affiliations

¹ TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: bscirica@bwh.harvard.edu.
² Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
³ Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁴ Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Science, Poznan, Poland.
⁵ Department of Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza, University of Palermo, Palermo, Italy; Unit of Clinical Nutrition, Obesity and Metabolic Diseases, University Hospital Policlinico "P. Giaccone," Palermo, Italy.
⁶ Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland.
⁷ Department of Diabetes and Nutrition Diseases, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj, Romania; Department of Diabetes, Nutrition and Metabolic Diseases, Cluj County Hospital, Cluj, Romania.
⁸ National Cardiology Research Center, Moscow, Russia.
⁹ Novo Nordisk A/S, Søborg, Denmark.
¹⁰ Saga University, Saga, Japan.
¹¹ Université de Franche-Comté, SINERGIES, Besançon, France.
¹² Department of Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
¹³ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹⁴ TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁵ Institute of Cardiovascular Science, University College London, London, United Kingdom.
¹⁶ Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

PMID: 39217559
DOI: 10.1016/j.jacc.2024.08.007

Abstract

Background: Patients with overweight and obesity are at increased risk of death from multiple causes, including cardiovascular (CV) death, with few therapies proven to reduce the risk.

Objectives: This study sought to assess the effect of semaglutide 2.4 mg on all-cause death, CV death, and non-CV death, including subcategories of death and death from coronavirus disease-2019 (COVID-19).

Methods: The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized 17,604 participants ≥45 years of age with a body mass index ≥27 kg/m² with established CV disease but without diabetes to once-weekly subcutaneous semaglutide 2.4 mg or placebo; the mean trial duration was 3.3 years. Adjudicated causes of all deaths, COVID-19 cases, and associated deaths were captured prospectively.

Results: Of 833 deaths, 485 (58%) were CV deaths, and 348 (42%) were non-CV deaths. Participants assigned to semaglutide vs placebo had lower rates of all-cause death (HR: 0.81; 95% CI: 0.71-0.93), CV death (HR: 0.85; 95% CI: 0.71-1.01), and non-CV death (HR: 0.77; 95% CI: 0.62-0.95). The most common causes of CV death with semaglutide vs placebo were sudden cardiac death (98 vs 109; HR: 0.89; 95% CI: 0.68-1.17) and undetermined death (77 vs 90; HR: 0.85; 95% CI: 0.63-1.15). Infection was the most common cause of non-CV death and occurred at a lower rate in the semaglutide vs the placebo group (62 vs 87; HR: 0.71; 95% CI: 0.51-0.98). Semaglutide did not reduce incident COVID-19; however, among participants who developed COVID-19, fewer participants treated with semaglutide had COVID-19-related serious adverse events (232 vs 277; P = 0.04) or died of COVID-19 (43 vs 65; HR: 0.66; 95% CI: 0.44-0.96). High rates of infectious deaths occurred during the COVID-19 pandemic, with less infectious death in the semaglutide arm, and resulted in fewer participants in the placebo group being at risk for CV death.

Conclusions: Compared to placebo, patients treated with semaglutide 2.4 mg had lower rates of all-cause death, driven similarly by CV and non-CV death. The lower rate of non-CV death with semaglutide was predominantly because of fewer infectious deaths. These findings highlight the effect of semaglutide on mortality across a broad population of patients with CV disease and obesity. (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity [SELECT]; NCT03574597).

Keywords: COVID-19; GLP1 receptor agonist; death; obesity.

Associated data

ClinicalTrials.gov/NCT03574597