“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 Ryan2024-08-30 (; similar)⁠:

Background: [more evidence on the special COVID-19/body-fat relationship] 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 COVID-19.

Method: The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial (NCT03574597) 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 mortality (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 incidence of 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.

Conclusion: 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.

Figure 1: Cumulative Incidence of All-Cause Death, CV Death, and Non-CV Death by Treatment. Cumulative incidence of (A) all-cause death, (B) cardiovascular (CV) death, and (C) non-CV death by treatment group. Data are for the full analysis set and from the in-trial observation period. Cumulative incidence estimates for time to CV death are modeled with all-cause death as competing risk, and time to non-CV death is modeled with CV death as competing risk using the Aalen-Johansen estimator. Deaths with insufficient data to be categorized were labeled as ‘undetermined cause of death’ and considered as ‘CV death’.