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J Am Coll Cardiol . The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial

tetano

Editor, Senior Moderator
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[SUP] 1 [/SUP], A Michael Lincoff[SUP] 2 [/SUP], Ildiko Lingvay[SUP] 3 [/SUP], Pawel Bogdanski[SUP] 4 [/SUP], Silvio Buscemi[SUP] 5 [/SUP], Helen Colhoun[SUP] 6 [/SUP], Anca-Elena Craciun[SUP] 7 [/SUP], Marat Ezhov[SUP] 8 [/SUP], Søren Hardt-Lindberg[SUP] 9 [/SUP], Ole Kleist Jeppesen[SUP] 9 [/SUP], Ana Laura S A Matos[SUP] 9 [/SUP], Koichi Node[SUP] 10 [/SUP], Francois Schiele[SUP] 11 [/SUP], Hermann Toplak[SUP] 12 [/SUP], André van Beek[SUP] 13 [/SUP], Peter E Weeke[SUP] 9 [/SUP], Stephen D Wiviott[SUP] 14 [/SUP], John Deanfield[SUP] 15 [/SUP], Donna Ryan[SUP] 16 [/SUP]



Affiliations
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/m[SUP]2[/SUP] 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.

 
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