Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
The Effect of Semaglutide on Mortality and COVID-19–Related Deaths
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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).
Additional Info
Disclosure statements are available on the authors' profiles:
The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial
J Am Coll Cardiol 2024 Aug 27;[EPub Ahead of Print], BM Scirica, AM Lincoff, I Lingvay, P Bogdanski, S Buscemi, H Colhoun, AE Craciun, M Ezhov, S Hardt-Lindberg, O Kleist Jeppesen, ALSA Matos, K Node, F Schiele, H Toplak, A van Beek, PE Weeke, SD Wiviott, J Deanfield, D RyanFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Many clinical trials did not survive the COVID-19 pandemic and were prematurely terminated due to poor enrollment or the inability to perform study procedures. The SELECT trial, which began in 2018, enrolled patients for more than a year when the COVID-19 pandemic struck. Despite these challenges, the SELECT investigators and participants diligently continued the trial. Recognizing the scientific importance of COVID-19 in high-risk patients with cardiovascular disease and overweight or obesity, they collected detailed information on COVID-19 and its complications.
Overall, 24.2% of participants reported a COVID-19 infection, with no difference between the semaglutide and placebo groups. Patients with COVID-19 infection were significantly more likely to die from noncardiovascular causes than those without COVID-19 (74.5% vs 32.5%). The majority of noncardiovascular deaths were directly related to COVID-19, with fewer deaths occurring in the semaglutide arm than in the placebo arm (43 vs 65; HR, 0.66; 95% CI, 0.44–0.96). As a result, noncardiovascular death acted as a “competing risk” for cardiovascular death and likely explained the unusual convergence of the cardiovascular event curves noted in the primary results publication.
There is much speculation on why semaglutide reduced the risk of COVID-19–related deaths. Although weight loss undoubtedly played a role, it may not have been the primary mechanism. Reductions in inflammation and improvements in kidney or liver function may have contributed to better health outcomes, allowing patients to avoid the worst COVID-19 complications. Regardless, these findings highlight that there is still much to learn about this classification of drugs and that the benefits go beyond improving only cardiovascular outcomes.