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J Am Coll Cardiol
. 2024 Aug 27:S0735-1097(24)08156-7.
doi: 10.1016/j.jacc.2024.08.007. Online ahead of print. The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial
Benjamin M Scirica 1 , A Michael Lincoff 2 , Ildiko Lingvay 3 , Pawel Bogdanski 4 , Silvio Buscemi 5 , Helen Colhoun 6 , Anca-Elena Craciun 7 , Marat Ezhov 8 , Søren Hardt-Lindberg 9 , Ole Kleist Jeppesen 9 , Ana Laura S A Matos 9 , Koichi Node 10 , Francois Schiele 11 , Hermann Toplak 12 , André van Beek 13 , Peter E Weeke 9 , Stephen D Wiviott 14 , John Deanfield 15 , Donna Ryan 16
Affiliations
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.
. 2024 Aug 27:S0735-1097(24)08156-7.
doi: 10.1016/j.jacc.2024.08.007. Online ahead of print. The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial
Benjamin M Scirica 1 , A Michael Lincoff 2 , Ildiko Lingvay 3 , Pawel Bogdanski 4 , Silvio Buscemi 5 , Helen Colhoun 6 , Anca-Elena Craciun 7 , Marat Ezhov 8 , Søren Hardt-Lindberg 9 , Ole Kleist Jeppesen 9 , Ana Laura S A Matos 9 , Koichi Node 10 , Francois Schiele 11 , Hermann Toplak 12 , André van Beek 13 , Peter E Weeke 9 , Stephen D Wiviott 14 , John Deanfield 15 , Donna Ryan 16
Affiliations
- PMID: 39217559
- DOI: 10.1016/j.jacc.2024.08.007
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.