Summary: A large randomized trial found that weekly injections of the weight‑loss medication Wegovy (semaglutide 2.4 mg) were associated with significantly lower mortality: COVID‑19–related deaths were reduced by about one‑third and overall deaths fell by roughly 19% compared with placebo.
The multicenter study followed more than 17,000 adults with established cardiovascular disease and overweight or obesity. Participants receiving semaglutide experienced fewer cardiovascular deaths and fewer non‑cardiovascular deaths, including deaths from infections such as COVID‑19.
Although infection rates were similar between the Wegovy and placebo arms, people treated with semaglutide had fewer severe COVID‑19 outcomes and deaths. Researchers emphasize that additional research is needed to clarify whether these benefits stem from weight loss, metabolic effects of semaglutide, or other mechanisms.
Key facts:
- Wegovy (semaglutide) was associated with a 33% lower risk of death due to COVID‑19 among trial participants who developed the infection.
- All‑cause mortality was reduced by about 19% with semaglutide versus placebo.
- The SELECT trial enrolled over 17,000 adults with cardiovascular disease and a body mass index ≥27 kg/m².
Source: Harvard
Overview of the trial findings
Researchers at Brigham and Women’s Hospital, affiliated with Harvard Medical School, analyzed mortality outcomes in the SELECT trial, which compared once‑weekly subcutaneous semaglutide 2.4 mg (Wegovy) with placebo. The trial ran from October 2018 through March 2023 and included 17,604 participants aged 45 and older with established cardiovascular disease and overweight or obesity but without diabetes. The average follow‑up was approximately 3.3 years.
Across the trial, a total of 833 deaths were adjudicated: 485 (58%) were cardiovascular and 348 (42%) were non‑cardiovascular. Participants randomized to semaglutide had lower rates of all‑cause mortality (hazard ratio [HR] 0.81; 95% CI 0.71–0.93), with reductions observed in both cardiovascular (HR 0.85; 95% CI 0.71–1.01) and non‑cardiovascular deaths (HR 0.77; 95% CI 0.62–0.95).
Infectious causes were the most frequent contributors to non‑cardiovascular deaths, and infectious deaths were fewer in the semaglutide group (62 vs. 87 events; HR 0.71; 95% CI 0.51–0.98). Although semaglutide did not reduce the incidence of COVID‑19 infection, among people who contracted COVID‑19 those treated with semaglutide had fewer serious adverse events related to COVID‑19 and fewer COVID‑19 deaths (43 vs. 65; HR 0.66; 95% CI 0.44–0.96).
The trial began before the COVID‑19 pandemic, so the observation that semaglutide was linked to fewer infection‑related and COVID‑19–related deaths was unanticipated. Investigators note it is uncommon for a cardio‑metabolic therapy to affect non‑cardiovascular outcomes so markedly.
These results do not prove causation for all observed effects and require replication. Planned and ongoing studies will examine possible biological mechanisms—whether benefits are driven predominantly by weight loss, improved cardiometabolic health, immunomodulatory effects, or other pathways—and whether similar drugs in this class show comparable effects.
Disclosures: Lead author Benjamin M. Scirica reports that institutional research grants to Brigham and Women’s Hospital have been received from several industry sources, and he discloses consulting fees and equity interests as described in the published report.
Funding: The study was funded by Novo Nordisk in collaboration with the academic steering committee; the sponsor contributed to study design, data collection, analysis, interpretation, and manuscript preparation in partnership with the investigators.
About this COVID‑19 and neuropharmacology research news
Author: BWH Communications
Source: Harvard
Contact: BWH Communications – Harvard
Image: The image is credited to Neuroscience News
Original research: “The Effect of Semaglutide on Mortality and COVID‑19–Related Deaths: An Analysis From the SELECT Trial” by Benjamin M. Scirica et al., published in the Journal of the American College of Cardiology (open access).
Abstract
The Effect of Semaglutide on Mortality and COVID‑19–Related Deaths: An Analysis From the SELECT Trial
Background
People with overweight and obesity face higher risks of death from multiple causes, including cardiovascular disease, and few therapies have been shown to lower overall mortality in this population.
Objectives
This analysis evaluated the effect of once‑weekly semaglutide 2.4 mg on all‑cause mortality, cardiovascular death, and non‑cardiovascular death, with particular attention to deaths caused by COVID‑19.
Methods
The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized 17,604 participants aged ≥45 years with a body mass index ≥27 kg/m² and established cardiovascular disease, but without diabetes, to once‑weekly subcutaneous semaglutide 2.4 mg or placebo. The mean follow‑up was 3.3 years, and adjudicated causes of death and COVID‑19 outcomes were collected prospectively.
Results
Among 833 total deaths, 485 were cardiovascular and 348 were non‑cardiovascular. Semaglutide was associated with lower all‑cause mortality (HR 0.81; 95% CI 0.71–0.93), lower non‑cardiovascular mortality (HR 0.77; 95% CI 0.62–0.95), and a trend toward fewer cardiovascular deaths (HR 0.85; 95% CI 0.71–1.01). Infection was the leading cause of non‑cardiovascular death and occurred less often in the semaglutide group.
While semaglutide did not prevent COVID‑19 infection, among those who contracted COVID‑19 there were fewer COVID‑19–related serious adverse events and fewer COVID‑19 deaths in the semaglutide arm.
Conclusions
In this large randomized trial of patients with cardiovascular disease and overweight or obesity, weekly semaglutide 2.4 mg reduced all‑cause mortality compared with placebo. The reduction in non‑cardiovascular deaths—primarily infectious deaths—contributed substantially to the overall mortality benefit. These findings underscore the potential mortality impact of semaglutide across a broad population and support further research into underlying mechanisms and broader clinical implications.