Semaglutide Reduces Rates of Cardiovascular, COVID-19-Related Deaths

A new study found semaglutide reduced rates of cardiovascular and COVID-19-related deaths among patients who were overweight.¹

People who are overweight or obese are at an increased risk of dying from various causes—including cardiovascular death—and few treatments exist to reduce the risk. Investigators aimed to evaluate the effect of semaglutide 2.4 mg on all-cause death, cardiovascular death, and non-cardiovascular death (i.e. COVID-19).

“These results are surprising. The trial started before COVID-19, and we never anticipated a global respiratory pandemic. We quickly recognized there was important data to be collected,” said lead investigator Benjamin M. Scirica, MD, MPH, director of quality initiatives at Brigham and Women’s Hospital’s Cardiovascular Division and Professor of Medicine at Harvard Medical School, in a statement.²

Due to the pandemic, COVID-19 ended up being a primary subcategory of non-cardiovascular death.¹ The study included 4258 patients (24.2%) with COVID-19.

SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients with Overweight or Obesity), a randomized, double-blind, placebo-controlled phase 3 trial, included 17,604 participants aged ≥ 45 years who had a body mass index (BMI) of ≥ 27 kg/m2 and cardiovascular disease. Participants were included if they had prior myocardial infarction, stroke, hospitalization for unstable angina pectoris, or a transient ischemic attack within 60 days before screening, as well as glycated hemoglobin ≥ 6.5%, history of type 1 or 2 diabetes, NYHA functional class IV failure, presence of end-stage kidney disease, or the need for chronic or intermittent dialysis.

Participants received either a once-weekly subcutaneous semaglutide 2.4 mg or a placebo; the mean trial duration was 3.3 years. In total, investigators examined 833 deaths, with 58% being cardiovascular deaths and 42% non-cardiovascular.

When compared with placebo, participants on semaglutide had 19% lower rates of all-cause death (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.71 – 0.93), 15% lower rates of cardiovascular death (HR, 0.85; 95% CI, 0.71 – 1.01), and 23% lower rates of non-cardiovascular death (HR, 0.77; 95% CI, 0.62 – 0.95). Among participants on semaglutide and placebo, the most common causes of cardiovascular death 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). As for non-cardiovascular deaths, infection was the most common cause (62 vs 87; HR, 0.71; 95% CI, 0.51 – 0.98).

Although semaglutide did not reduce incident COVID-19 (P = .46), participants with COVID-19 who were on semaglutide had fewer COVID-19-related serious adverse events (232 vs 277; P = .04) or deaths than participants on placebo (43 vs 65; HR, 0.66; 96% CI, 0.44 – 0.96). In general, during the COVID-19 pandemic, fewer patients on semaglutide than on placebo had infectious deaths.

Investigators observed patients who died of COVID-19 had a change in weight from randomization to the time they reported COVID-19 of -6.4 kg in the semaglutide group and -0.9 kg in the placebo group (P < .001). Patients who did not die of COVID-19 had a weight change of -8.4 kg and -1.25 in the semaglutide and placebo arms, respectively (P < .001).

Investigators noted that they did not know if the benefit of semaglutide was due to its weight loss prosperities or other effects. The team said the findings would need to be replicated with another trial and further studies should explore the potential mechanisms of action. They also pointed out how the findings were limited because cardiovascular death did not meet the prespecified P value.

“It is rare for a cardio-metabolic drug to modify non-cardiovascular outcomes,” Scirica said.² “The fact that semaglutide reduced non-cardiovascular death, and in particular COVID-19-related deaths, was surprising. It opens up new avenues for exploring how this class of drugs may benefit patients.”

References

1. ^{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. Published online August 27, 2024. doi:10.1016/j.jacc.2024.08.007}
2. ^{Brigham-Led Study Finds Weight Loss Drug Semaglutide Reduced COVID-19 Related Deaths During The Pandemic. EurekAlert! August 30, 2024. https://www.eurekalert.org/news-releases/1056309. Accessed September 6, 2024.}