Wegovy linked to fewer COVID-19-related deaths vs. placebo in SELECT population
Click Here to Manage Email Alerts
Key takeaways:
- For patients with overweight or obesity and CVD but not diabetes, Wegovy reduced risk for death from COVID-19 vs. placebo.
- The Wegovy group had reduced risk for all-cause and non-CV death.
In an analysis of deaths of patients with obesity but not diabetes from the SELECT trial, those assigned semaglutide 2.4 mg had reduced risk for death from COVID-19 compared with those assigned placebo.
The semaglutide 2.4 mg (Wegovy, Novo Nordisk) group also had lower rates of all-cause death and non-CV death compared with the placebo group, according to the findings presented at the European Society of Cardiology Congress and simultaneously published in the Journal of the American College of Cardiology.
As Healio previously reported, the SELECT trial included 17,604 patients (27% women) with BMI 27 kg/m2 or more (mean, 33.3 kg/m2) aged 45 years or older (mean, 61 years) with established CVD but no diabetes. In the main results, semaglutide 2.4 mg reduced risk for CV death, MI and stroke by 20% compared with placebo.
The present analysis concerned the 833 patients who died during a mean follow-up of 3.3 years.
“We know that patients with overweight and obesity are at increased risk of death from multiple causes, not just cardiovascular death, and few therapies have been proven to reduce risk,” Benjamin M. Scirica, MD, MPH, professor of medicine at Harvard Medical School, director of quality initiatives at Brigham and Women’s Hospital’s Cardiovascular Division and a senior investigator at the Thrombolysis and Myocardial Infarction (TIMI) Study Group, said during a presentation. “The COVID-19 pandemic was obviously unanticipated and began over 1 year after the SELECT trial started, but it provided the opportunity to evaluate the effect of COVID-19 on patients at high risk of COVID-19 complications and death, given their underlying comorbidities.”
Lower rates of death
Among the deaths, 58% were from CV causes, according to the researchers.
Compared with the placebo group, the semaglutide group had significantly lower rates of all-cause death (HR = 0.81; 95% CI, 0.71-0.93) and non-CV death (HR = 0.77; 95% CI, 0.62-0.95) and a numerically lower rate of CV death (HR = 0.85; 95% CI, 0.71-1.01), Scirica and colleagues found.
The most common causes of CV death were sudden cardiac death (semaglutide, 98; placebo, 109; HR = 0.89; 95% CI, 0.68-1.17) and undetermined death (semaglutide, 77; placebo, 90; HR = 0.85; 95% CI, 0.63-1.15), whereas the most common cause of non-CV death was infection, which happened less often in the semaglutide group (62 deaths vs. 87 deaths; HR = 0.71; 95% CI, 0.51-0.98), according to the researchers.
Semaglutide did not reduce the incidence of COVID-19, but the semaglutide group had fewer COVID-19-related serious adverse events (232 vs. 277; P = .04) and fewer COVID-19-related deaths (43 vs. 65; HR = 0.66; 95% CI, 0.44-0.96).
“The lower rates of noncardiovascular death with semaglutide were predominantly due to fewer infectious deaths and in particular COVID-19-related deaths during the pandemic,” Scirica said during the presentation. “Noncardiovascular death therefore acted as a competing risk for cardiovascular death in this study and may explain the convergence of the cardiovascular death curves that we saw. Mechanisms to explain this finding remain speculative, and are hard to answer. But overall, these findings reinforce that overweight and obesity increase the risk of death due to many etiologies, which may be modified by treatment with incretin-based therapies such as semaglutide.”
‘Synergistic benefits’
In a related editorial published in JACC, Jeremy Samuel Faust, MD, MS, emergency physician at Brigham and Women’s Hospital and instructor at Harvard Medical School, wrote that “by adding documentation of COVID-19 cases and mortality, the SELECT trial has yielded important insights regarding the epidemiology of COVID-19 and the very nature of infectious disease mortality.
“If confirmed, the magnitude of the reductions in contemporaneous all-cause and COVID-19-specific mortality among semaglutide recipients compared to placebo ... closely resembles the synergistic benefits of aspirin and percutaneous coronary interventions for patients with acute ST-segment elevation myocardial infarction,” he wrote.
References:
- Faust JS. J Am Coll Cardiol. 2024;doi:10.1016/j.jacc.2024.08.035.
- Scirica BM, et al. J Am Coll Cardiol. 2024;doi:10.1016/j.jacc.2024.08.007.
Perspective
Back to Top
Harlan M. Krumholz, MD, SM, FACC
Studies like this one indicate to us that this is not just about weight loss. This is really about promotion of health. What we are finding is that these drugs are having a dramatic impact on cardiovascular health, and I speculate that this sort of marked improvement in cardiometabolic health is somehow protecting people when they’re in a position where they need to defend themselves against something like a novel virus.
This is an amazing study. The fact that it was embedded in a randomized trial for another purpose, and the researchers had the agility to say, we can learn something about the pandemic, is extraordinary. They were probably thinking at the beginning that this is going to blow up the trial, because this competing risk is going to interfere with our ability to detect what we thought we were going to find, which is that the treatment for obesity of high-risk patients with CVD with semaglutide is going to drive a reduction in CV events; this population is enriched for people whose most important risk is CVD. That’s going to be the premise for a positive trial.
In this trial, it turned out that COVID-19 was the third leading cause of death. An unexpected competing risk loomed over everyone in the trial. But the researchers were smart enough to collect the data about infections and COVID-19-related adverse events. Although there was no difference in reported infections, there was a marked benefit in terms of not suffering the consequences of the infection to such a great extent.
We knew before that obesity is a risk factor for adverse events in COVID-19. We saw it especially in the early, harrowing days of the pandemic. But we didn’t know that if you were to treat the obesity, that it would put people in a position where they would be protected. Likely, that was more about the cardiometabolic derangements than the people.
We are not even certain how these drugs work. What we do know from other studies is that they can reduce the body’s baseline inflammation, and they do it independent of the weight loss. There’s something interesting going on here, not only with cardiometabolic health, but with inflammation levels in the body, which may be related to the immune system itself. So I conceptualize these drugs as health promoters; they can treat obesity but have beneficial effects in other ways we are still trying to understand. But the evidence is coming out very strongly that these drugs are promoting health generally. The more we can get people healthy, it benefits them in terms of many risks beyond CV risk.
This study is another reason among many that we should give our patients the option to treat their obesity and put themselves in a position where they are healthier. We know from several studies that the treatment of obesity can help in many dimensions, from CVD to heart failure with preserved ejection fraction to chronic kidney disease. Now we know that for people with obesity and cardiometabolic derangements, we can make them healthier and better able to resist infections.
A question will be how broad-based this is. During the pandemic, influenza went down, but it is also a big threat to people with HF or CVD. It will be interesting to see if this is a broad-based protection against stresses the body gets.
It creates an imperative that we need to be sure that everyone who has obesity has the opportunity to be treated. For people in the U.S. who don’t have good insurance or access, we have to work to improve those. This is now one of the best-studied drugs we have, and almost at every turn, we are finding benefits, with a big margin of net benefit. We need to think about making sure people get access.
Collapse
Scirica BM, et al. Clinical trial updates on the GLP-1 receptor agonist, semaglutide. Presented at: European Society of Cardiology Congress; Aug. 30-Sept. 2, 2024; London (hybrid meeting).
Read more about
Click Here to Manage Email Alerts