By Stan Deresinski, MD, FACP, FIDSA
SYNOPSIS: Semaglutide recipients who developed COVID-19 had significant protection against the occurrence of adverse outcomes, including death.
SOURCE: Scirica BM, Lincoff AM, Lingvay I, et al. 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. [Online ahead of print].
The SELECT trial was a multicenter, double-blind, Phase III, randomized trial comparing semaglutide administration (2.4 mg once weekly) in individuals 45 years of age or older with a body mass index ≥ 27 kg/m2 with cardiovascular (CV) disease but without diabetes mellitus.1 In the study, semaglutide reduced all-cause mortality by 19%, a reduction driven by both CV and non-CV death, with reductions of 15% and 23%, respectively. Study procedures were affected by the intervention of the COVID-19 pandemic. The analysis by Scirica and colleagues examines the outcomes of COVID-19 occurring in the study participants.
Overall, there were 833 deaths among the total of 17,604 subjects over a mean trial duration of 3.3 years, with statistically significant decreased overall mortality and non-CV deaths in the semaglutide recipients. The most common cause of non-CV death was infection, which occurred less frequently in semaglutide recipients than in placebo recipients (62 vs. 87; hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.98). Although there was no significant difference in the occurrence of COVID-19, among those who did develop this infection, semaglutide receipt was associated with fewer COVID-19-related serious adverse events (232 vs. 277; P = 0.04) and deaths (43 vs. 65; HR, 0.66; 95% CI, 0.44-0.96).
Commentary
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with widespread use in the treatment of diabetes mellitus and obesity. Obesity is a known risk factor for adverse outcomes in patients with COVID-19. Of note is that semaglutide was associated with a 6.4-kg weight loss compared to 0.9 kg in placebo recipients (P < 0.001) among patients who died, with a similar difference among survivors. Weight loss improves multiple aspects of health, and bariatric surgery is associated with reduced complications of COVID-19. Obesity is associated with increased inflammation, which is reduced with weight loss and with semaglutide administration.2
This study demonstrates that we can add protection against COVID-19-related adverse outcomes, including death, to the previously identified benefits of semaglutide therapy. In addition to the treatment of diabetes mellitus and obesity, these include a reduction in cardiovascular events, including heart failure, renal disease, and dementia. Other drugs, such as tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, may have similar effects.
Stan Deresinski, MD, FACP, FIDSA is Clinical Professor of Medicine, Stanford University.
