Semaglutide Reduces Cardiovascular and COVID Death

Injectable medications to manage overweight, obesity, and diabetes have made countless headlines since they were introduced. They have been a popular and effective way for many people to lose weight or control their blood sugar.

Continuing research has shown that one of those medications has additional unexpected benefits. A new study from Mass General Brigham shows that semaglutide reduced people’s risk of death from any cause. People taking this medication were significantly less likely to die of cardiovascular events and infectious diseases, particularly COVID. The dose used in this trial was the highest dose, sold as Wegovy. Lower doses, sold as Ozempic or Rybelsus, are used in patients with diabetes.

“Obesity and overweight are risk factors for worse outcomes from respiratory diseases like COVID and cardiovascular conditions such as heart attack and stroke,” says Benjamin Scirica, MD, a Mass General Brigham cardiologist. “Semaglutide is often thought of first as a weight loss drug. But data from this study and others highlight the fact that it also improves overall cardiovascular risk and lowers the risk of non-cardiovascular events.”

Dr. Scirica cares for patients at Brigham and Women’s Hospital and was first author on the new study.

Weight loss drug mimics digestive hormone

After you eat food, your body releases a hormone called glucagon-like peptide-1 (GLP-1). Semaglutide mimics this hormone. It helps the body produce insulin and lower blood sugar levels. It also likely has many other effects on different parts of the body, notes Dr. Scirica.

People can take the prescription medication by mouth every day or self-inject it weekly. Most start with a low dose and increase the dose over time.

SELECT trial shows lower rates of cardiovascular death

A great deal of research has shown that people with overweight or obesity have increased risk of premature death from various causes. The SELECT trial set out to explore whether semaglutide affects a person’s risk of death from cardiovascular causes.

The study included 17,604 people who were at least 45 years old and had a body mass index greater than or equal to 27. Participants had existing cardiovascular disease but not diabetes. They received one of two treatments:

1. The maximum weekly dose of 2.4 mg of semaglutide by injection

2. A placebo (a fake treatment that looked like semaglutide but had no effect)

The study found that deaths from cardiovascular causes were 15% lower in the semaglutide group.

People taking semaglutide also had lower rates of COVID complications.

A year after the study began, the COVID-19 pandemic struck. The researchers decided to collect data on COVID infections and deaths. They simply wanted to document whether the viral infection was affecting their findings.

About 1 in 4 patients in the study developed COVID infection. The researchers compared the semaglutide group and the placebo group. They found that semaglutide didn’t protect people against COVID infection, but it was associated with significantly fewer complications and deaths.

Deaths from non-cardiovascular reasons (including all infections) were 23% lower in the semaglutide group. COVID death rates were 19% lower in the treatment group.

Potential semaglutide health benefits

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

• Better overall health: Semaglutide has been associated with better health and function of several organs, including the heart, liver, and kidneys. For example, in the FLOW and SELECT studies, semaglutide improved kidney outcomes and reduced death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease.

• Less inflammation: Semaglutide reduces inflammation throughout the body. 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 deaths, and a lot of the drugs that were used and tested in the sickest patients with COVID were anti-inflammatory drugs,” he says. “Semaglutide may have lowered the inflammatory state of the body and made people a little healthier when they developed COVID.”

• Lower BMI: Higher body mass index (BMI) is associated with an increased risk of COVID infection, complications, and death. Some research has shown that weight loss after bariatric surgery can help protect people from those complications. People in the SELECT study taking semaglutide lost about 15 pounds, lowering their BMI and possibly protecting themselves from the worst COVID outcomes.

“Patients who were treated with semaglutide were likely in a healthier state when they developed COVID, and therefore their bodies were able to prevent these serious complications,” Dr. Scirica says.

A new tool to improve and protect health

Dr. Scirica encourages health care providers and patients to consider semaglutide as more than just a weight loss drug. He says the SELECT study shows that it can be another tool to improve and protect their overall health.

“Many people with established heart or vascular disease are doing everything they can to lower risk of cardiovascular disease — making sure cholesterol is under control, making sure blood pressure is in the optimal range, smoking cessation, preventing diabetes,” he says. “Taking semaglutide is now one additional avenue to try to maximize one’s chances of preventing future events. It’s saying, ‘I want to do everything possible to try to reduce my risk of future heart events and COVID complications.’”

He encourages people already taking semaglutide to be aware of the benefits they may not be able to see.

“These protective effects don’t seem to be dependent on weight — even people who did not have significant weight loss still benefited in terms of fewer heart attacks, strokes, or dying,” Dr. Scirica says. “So we don’t want people to get frustrated or stop taking these drugs if they are not seeing results on the scale as quickly as they would like.”