Why Your Cardiologist May Prescribe Semaglutide (Wegovy)

[Originally published: March 11, 2024. Updated: April 2, 2024.]

Can a popular anti-obesity medication lower your chances of a heart attack, stroke, or cardiovascular death? In March, the Food and Drug Administration (FDA) approved semaglutide (brand name: Wegovy®) for just that purpose after a study published last November showed that the medication lowers certain people’s risk for those events by as much as 20%. People can now take this medication if they have obesity or overweight and have cardiovascular disease. A separate study by Yale researchers showed that as many as 6.6 million Americans fit these criteria.

Semaglutide attracted considerable attention in 2017 when the medication, given weekly by self-injection under the brand name Ozempic®, received FDA approval for lowering blood sugar in people with type 2 diabetes. Later, its label was expanded, through an FDA approval, to include a reduction in the risk of major heart events in the same group. In 2021, the FDA gave the green light to Wegovy to help people with obesity or overweight lose weight. (Ozempic and Wegovy are both the same molecule—semaglutide—and are made and sold by Novo Nordisk.)

In 2023, a clinical trial called Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) showed that Wegovy can significantly reduce the risk of major heart events—this time in people with extra weight and a cardiovascular condition who don’t have diabetes. Now, the FDA has expanded Wegovy’s approval to help this group.

“The SELECT trial is a major breakthrough,” says Yale Medicine cardiologist Harlan Krumholz, MD, SM, explaining that while semaglutide [given as Ozempic] was already known to lower the risk of heart disease in people with diabetes, the SELECT trial was the first to show that Wegovy, which contains a higher dose of semaglutide, also lowers that risk even in people who don’t have diabetes. “And there is an enormous number of Americans who are eligible for this,” says Dr. Krumholz, who is also director of the Center for Outcomes Research and Evaluation (CORE).

A majority of people with cardiovascular disease do not have diabetes, adds Ania Jastreboff, MD, PhD, a Yale Medicine endocrinologist, who is an expert in obesity medicine and director of the Yale Obesity Research Center (Y-Weight). “The lifetime risk of cardiovascular disease in people with obesity but without diabetes is about one in two women and about two in three men,” she says. “The results from the SELECT trial are a call to action.”

Below, Yale Medicine experts answer four questions about Wegovy and cardiac risk.

Wegovy is a GLP-1 receptor agonist anti-obesity medication that has several cardiovascular benefits, based on data from the SELECT Trial published last fall in The New England Journal of Medicine. The trial tracked 17,604 adults ages 45 and older who had overweight or obesity and a cardiovascular condition, but no history of diabetes. These adults were given either 2.4mg of semaglutide (Wegovy) weekly or a placebo for an average of about three years.

In addition to having a 20% lower risk overall of major cardiac events, such as heart attack, stroke, or cardiovascular death, participants who took Wegovy had a 28% reduction in heart attacks (for those already taking heart medications, such as statins, to reduce cholesterol), a 7% decrease in non-fatal strokes, and a 15% drop in cardiovascular-related deaths.

There was one non-heart-related finding: Among those who took Wegovy, there was a 19% lower death rate from any cause.

Obesity or overweight affects more than 70% of American adults, and both are considered serious health issues that increase the risk for premature death and a variety of health problems, including heart attack and stroke. “The thinking is that if obesity is treated early, these cardiovascular-related benefits will start to occur even in the first three years,” Dr. Krumholz says. “This could mean that even more benefit will accrue over the long-term.”

At this point, no one can say for sure why semaglutide prevents secondary cardiovascular events—scientists are still studying whether there are other factors in addition to weight reduction. The SELECT study also did not show whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in people who do not already have a cardiovascular condition. “But future studies may show that people with obesity, even without heart disease, have meaningful reductions in their risk for major cardiovascular disease,” Dr. Krumholz says.

A follow-up study by Yale, published in Circulation: Cardiovascular Quality and Outcome, estimated that 6.6 million Americans with obesity and cardiovascular conditions, but not diabetes, could benefit from Wegovy. To arrive at their estimate, researchers combed through national registries, looking for people with the same characteristics as those in the SELECT trial and extrapolating that representative group to the population of the entire nation.

Because Wegovy has the potential to help such a large number of people, making it more available and accessible could change how cardiovascular disease is treated, Dr. Krumholz explains.

“We’ve been stymied over the last decade in cardiology,” Dr. Krumholz says. “Our progress against heart disease slowed and even reversed, and the obesity epidemic has been a main contributor to that. But we lacked a way to target it directly.”

As a result, doctors focused on treating heart-related conditions like high blood pressure and high cholesterol. “Now, we may be able to treat obesity directly, which could turn the tide on the current trends in heart disease.”

The FDA cautions that Wegovy carries the risk of such side effects as nausea, diarrhea, constipation, and vomiting; low blood sugar in people taking certain other medications for diabetes; pancreas or gallbladder problems; eye problems in people with diabetes; and suicidal behavior or thinking. About a third of the SELECT trial participants reported serious side effects, and about 17% in the group that took Wegovy and 8% of those who received a placebo left the study for that reason.

However, Dr. Krumholz says most people tolerate the drug well when administered gradually, increasing the dose a little every week. “The trial data is strong and convincing, and there's already a long line of safety and efficacy evidence from people with diabetes who have taken the drug,” he says.

Ozempic was already available for lowering the risk of major adverse cardiovascular events in patients with diabetes who have established cardiovascular disease and have obesity or overweight, with an initial body mass index (BMI) of 27 or greater. This latest approval for Wegovy simply allows doctors to formally expand treatment to a larger group of people: those with overweight or obesity who have cardiovascular disease but not diabetes. (Some doctors had been prescribing Wegovy “off-label” for this purpose. This approval may increase the chances that insurance companies will cover the cost of the medication prescribed for heart-health benefits.)

“The bigger issue is financial barriers,” Dr. Krumholz says, noting that Wegovy is expensive and out of reach for many people without health insurance or financial resources. This has been an issue for higher numbers of American adults who are Black or Hispanic, according to a 2022 article in the Journal of the American Heart Association (JAHA), on which Dr. Krumholz was a contributor.

The list price for Wegovy is $1,349 for a 28-day supply. “We need to make sure that everyone who can benefit from these medications has access to them,” Dr. Krumholz says. “The hope with this latest approval for heart health is that more insurance companies will provide greater coverage, which would be a good first step.”

In late March, the Centers for Medicare and Medicaid Services issued new guidance saying Medicare Part D plans can start covering anti-obesity drugs if they are also approved for an added health benefit, such as heart health.

Visit the Yale Obesity Research Center (Y-Weight) to learn more about Yale School of Medicine’s ongoing research on anti-obesity drugs and how they can help people with obesity.