Weight-loss drug tied to lower risk of death from COVID, heart disease, all causes

COVID-19
Semaglutide injectors in box

aprott / iStock

The anti-obesity drug semaglutide may lower the risk of death from COVID-19, cardiovascular disease, and all causes, according to a randomized controlled trial published late last week in the Journal of the American College of Cardiology (JACC).

Researchers with the ongoing, multinational Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity (SELECT) trial randomly assigned 17,604 participants aged 45 years or older who were overweight or obese and had cardiovascular disease but not diabetes to receive a weekly injection of 2.4 milligrams of semaglutide or a placebo. 

The study period was October 2018 to March 2023, average follow-up was 3.3 years, and all participants had a body mass index of at least 27 kilograms per square meter [kg/m2]).  

"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," the researchers wrote.

The study was funded by semaglutide maker Novo Nordisk. Semaglutide is sold under the brand names Ozempic, Wegovy, and Rybelsus.

Drug didn't reduce COVID infections

In total, 833 participants died (58% from CV disease and 42% from non-CV conditions). Participants in the semaglutide group had lower rates of all-cause death (19% reduction), CV death (15%), and non-CV death (23%) than placebo recipients.

The most common causes of CV death among semaglutide (versus placebo) recipients were sudden cardiac death (98 vs 109; 11% reduction in semaglutide recipients) and undetermined causes (77 vs 90; 15%). Infection was the most common cause of non-CV death and occurred at a lower rate among semaglutide than placebo recipients (62 vs 87; 29%). 

A total of 24.2% of participants tested positive for COVID-19. Semaglutide wasn't linked to a lower rate of COVID-19 infection, but fewer infected participants who received semaglutide had COVID-related serious adverse events (2.6% vs 3.1%) or died (43 vs 65; 44% reduction). 

Patients diagnosed as having COVID-19 were more likely to die of a non-CV cause than a CV cause (74.5% vs 25.5%), while the relationship was the inverse in patients without COVID-19 (32.5% non-CV vs 67.5% CV deaths).

The change in weight between randomization and COVID-19 infection in participants who died of their infections was −6.4 kg (14.1 pounds) in the semaglutide group, compared with −0.9 kg (2 pounds) in the placebo group and −8.4 kg (18.5 pounds) vs −1.25 kg (2.8 pounds), respectively, in participants who survived.

'Akin to a vaccine' against effects of a pathogen

"It is rare for a cardio-metabolic drug to modify non-cardiovascular outcomes," lead author Benjamin Scirica, MD, MPH, director of quality initiatives at Brigham and Women's Hospital's Cardiovascular Division, said in a Brigham news release. "The fact that semaglutide reduced non-cardiovascular death, and in particular COVID-19-related deaths, was surprising."

The present study implies that, in just a short period, semaglutide was adequate to reduce SARS-CoV-2 mortality.

Jeremy Faust, MD

In an American College of Cardiology news release, Harlan Krumholz, MD, JACC editor-in-chief and professor at the Yale School of Medicine, said, "The ability of semaglutide to significantly lower cardiovascular and COVID-19-related adverse events underscores the transformative potential of targeting obesity and improving cardiometabolic health as a strategy to protect against a broad spectrum of health threats." Krumholz wasn't involved in the study.

The SELECT trial began before the COVID-19 pandemic began, so the researchers modified the protocol to document COVID-19 infections, adverse events, and deaths. The authors said the reduction in non-CV deaths, especially those due to infection, may have been detectable only due to COVID-19 surges in non-CV deaths.

In a related JACC commentary, Jeremy Faust, MD, of Brigham and Women's Hospital, said the continuation of the trial throughout the pandemic and the focus on a population at high risk for poor COVID-19 outcomes facilitated the discovery, the magnitude of which "closely resembles the synergistic benefits of aspirin and percutaneous coronary interventions for patients with acute ST-segment elevation myocardial infarction."

Faust said that the lives of people who had fatal heart attacks precipitated by the stress and inflammatory response to COVID-19 or other infections perhaps could have been saved if they had taken semaglutide.

"The present study implies that, in just a short period, semaglutide was adequate to reduce SARS-CoV-2 mortality," he said. "This is akin to a vaccine against the indirect effects of a pathogen, except here, we would expect the efficacy to augment over time, rather than wane. Moreover, the benefit could apply to many infections, not just SARS-CoV-2."

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