In this Article:

• People who are overweight or obese have an increased risk of premature death from various causes.
• A recent study found that people taking semaglutide had a lower risk of death from COVID-19 and other causes.
• Potential mechanisms of action may include lower BMI, reduced inflammation, or better overall health.
• The SELECT study and others suggest that semaglutide should be considered a cardiometabolic drug that lowers the risk of cardiovascular and non-cardiovascular events.

A new study from Mass General Brigham shows that people taking semaglutide, known primarily as a weight-loss and diabetes drug, were less likely to die from any cause. This included deaths from cardiovascular disease and, surprisingly, COVID-19.

“These results were unexpected, to say the least,” says Benjamin Scirica, MD, a cardiologist at Brigham and Women’s Hospital and first author on the study. “This drug is often thought of first as a weight loss drug. But data from this study and others highlight that it should be thought of primarily as a cardiometabolic drug that improves overall cardiovascular risk and lowers the risk of non-cardiovascular events.”

Semaglutide Reduces Risk of Cardiovascular and Non-Cardiovascular Death

Research has long shown that people with overweight or obesity have an increased risk of premature death from various causes. The SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) began in 2018 to explore semaglutide’s effects on cardiovascular deaths.

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist sold under the brand names Ozempic and Rybelsus for diabetes and the brand name Wegovy for weight loss, mimics a hormone released in the gastrointestinal tract when a person eats. GLP-1 medications make the body produce more insulin, reducing blood glucose.

SELECT studied 17,604 people who were at least 45 years of age with a BMI greater or equal to 27. Participants also had to have cardiovascular disease but not diabetes. People in the study received either a placebo or a weekly dose of 2.4 milligrams of subcutaneous semaglutide.

When the COVID pandemic began, the researchers decided to collect data on COVID-19 infections and complications as well.

“We realized it was a unique opportunity to understand how a respiratory pandemic would affect a group of high-risk individuals,” Dr. Scirica recalls. “These were the type of patients who, when they were hospitalized with COVID-19, had some of the worst outcomes.”

About a quarter of the patients in the study developed COVID-19 infection. Semaglutide wasn’t protective against COVID-19 infection, but it was associated with significantly fewer complications and deaths.

In results reported at the European Society of Cardiology Congress 2024 and published in the Journal of the American College of Cardiology, the investigators identified 833 deaths in the patient group. Death rates from COVID-19 were 19% lower in those taking semaglutide versus placebo. Deaths from cardiovascular causes were 15% lower in the semaglutide group. Deaths from non-cardiovascular reasons (including infectious reasons such as COVID-19) were 23% lower.

How a Weight-Loss Drug Might Work to Reduce COVID Deaths

Dr. Scirica offers several potential reasons for the COVID-19 finding. “We can’t exclude chance, but there are a couple of plausible hypotheses why this may be a real signal,” he says.

Higher BMI is associated with an increased risk of complications and death in people who contract COVID-19. Some research has shown that bariatric surgery is protective against COVID-19 complications. People in this study taking semaglutide lost about 7 kilograms, lowering their BMI and potentially protecting themselves from worse outcomes.

Dr. Scirica also emphasizes the potential role of reduced inflammation with semaglutide. The SELECT study measured blood levels of C-reactive protein (CRP), which increases in the presence of inflammation in the body. Patients taking semaglutide had significantly reduced levels of that marker.

“We knew that inflammation was key to some of the worst outcomes in COVID-19 deaths, and a lot of the drugs that were used and tested in the sickest patients with COVID were anti-inflammatory drugs,” he says. “So being on semaglutide may have lowered the inflammatory state of the body and made people, therefore, a little healthier when they developed COVID.”

Finally, semaglutide has been associated with better health and function of several organs, including the heart, liver, and kidneys. “Patients who are treated with semaglutide just were in a healthier standpoint when they developed COVID; therefore, their bodies were able to prevent these serious complications,” Dr. Scirica says.

The Future of GLP-1 for Heart Health and Overall Health

Because SELECT studied semaglutide at its highest dose, the results cannot necessarily be extrapolated to other similar drugs or other doses. Dr. Scirica is eagerly awaiting further analyses from other studies of semaglutide in high-risk patients conducted during the pandemic, including FLOW (Evaluate Renal Function with Semaglutide Once Weekly) and SOUL (Semaglutide cardiOvascular oUtcomes).

FLOW found that semaglutide improved kidney outcomes and reduced death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. Data regarding infectious outcomes are pending. SOUL is exploring semaglutide’s effects in people with atherosclerotic CV disease and/or chronic kidney disease.

In the meantime, Dr. Scirica encourages healthcare providers and patients to consider the drug as a tool for more than just weight loss.

“Many people with established heart disease or heart or vascular disease are doing everything they can to try to help improve their health and reduce their cardiovascular risk. We talk a lot about reducing the traditional risk factors—making sure that cholesterol is under control, making sure blood pressure is in the optimal range, smoking cessation, preventing diabetes. These are all sort of the core risk-reducing activities we advise,” he says. “Taking semaglutide, up to 2.4 milligrams, is now one additional avenue to try to maximize one’s chances of preventing future events.”