Popular weight-loss drug Wegovy now approved for heart disease. Here's what we know.

The drug semaglutide, sold commercially as Ozempic or Wegovy, is well known for helping people lose significant amounts of weight quickly. Now the U.S. Food and Drug Administration has approved Wegovy, the version of semaglutide currently prescribed for weight loss, for preventing serious cardiovascular conditions in certain people who are at high risk.

The FDA's March 8 announcement will allow doctors to prescribe Novo Nordisk's Wegovy, which has a higher maximum dose of semaglutide than Ozempic does, to people who are overweight or obese and have had at least one cardiovascular event such as a heart attack or stroke. "It opens up a whole new group of patients for us," says Nicholas Marston, a cardiologist at Brigham and Women's Hospital.

Here's what we know about semaglutide's effects on cardiovascular disease and how it might work.

Who's a good candidate for taking the drug to reduce cardiac risk?

The FDA's approval expands the use of semaglutide to people with a BMI of 27 or higher (qualified as overweight or obese) with a history of cardiac events. But it's unknown whether the drug would work as well at preventing cardiovascular disease in people with lower BMIs. And it still hasn't been tested in people who may be at risk of cardiovascular disease but have not been diagnosed.

How effective is semaglutide at preventing cardiovascular problems?

The FDA based its decision on a 2023 trial called Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT), in which Novo Nordisk tested Wegovy in more than 17,000 people. The participants all had a body mass index (BMI) of 27 or higher. But unlike previous trials of semaglutide, the SELECT participants did not have a history of diabetes, the disease for which the drug was initially approved in 2017.

The trial showed that people who took semaglutide lost almost 10% of their body weight on average compared to people who received a placebo. They had a 20% lower risk of heart attacks and strokes in the course of about three years, as well as significantly lower cholesterol and blood pressure.

In light of these findings, which were published in November, the FDA's decision to approve the drug for preventing heart problems "wasn't surprising at all," says Joseph Wu, a cardiologist at Stanford University. He says the 20% reduction in risk is impressive. By comparison, a 2023 trial of another new heart drug, bempedoic acid, found a 13% reduction in risk of heart attacks and strokes over three years. Wegovy may join the ranks of other effective cardiovascular drugs, such as beta blockers and statins.

How does the drug prevent cardiac problems?

In general, semaglutide is thought to cause people to lose weight by binding to a molecule on cell surfaces called the GLP-1 receptor, where it mimics a hunger hormone and slows the rate at which the stomach empties. This reduces appetite and causes people to eat less, resulting in rapid weight loss.

But its effects on the cardiovascular system are less clear. "It's the $1-million question," Wu says. Weight loss probably accounts for the majority of the effect, he says. Researchers already know that, for people who are overweight, losing 10% of one's body weight significantly reduces the risk of cardiovascular disease and stroke, and it has other benefits such as reducing knee pain and shortness of breath.

It's possible that semaglutide is also having another effect, Wu and Marston say. The drug may bind to GLP-1 receptors or some other target directly on the heart or blood vessels and affect their function or reduce inflammation that could damage the cardiovascular system. The SELECT trial found evidence that the drug lowered blood pressure, inflammation (as measured by blood proteins made by the liver) and cholesterol.

Figuring out how much of the effect is a result of weight loss or an additional effect will likely be a research priority in the future, Marston says. "We always like to understand why something works." Scientists will be able to test some of these questions in the lab using human cells or animal models to understand semaglutide's mechanism for preventing cardiovascular disease more precisely. And the SELECT trial has given Novo Nordisk a massive dataset that the company can mine for more information about the drug's effects.

What are the side effects?

Semaglutide is not a new drug, and its side effects and risks are well known. The most common ones are gastrointestinal problems such as nausea and constipation, which occur because the drug slows gastric emptying.

But researchers haven't yet studied what will happen to cardiovascular risk if people stop taking the drug. People who take semaglutide for weight loss but discontinue it usually gain the weight back quickly, which Wu says would likely increase their cardiovascular risk to what it was previously. "The main message is: taking this medication doesn't mean you no longer need to lead a healthy lifestyle," he says.

What do scientists still not know about semaglutide and heart disease?

 Wu says it's still unclear whether losing 10% of one's weight without weight loss drugs has a different effect on cardiovascular risk than losing it with semaglutide; no one has done a head-to-head comparison. And he adds that the SELECT trial did not include many participants from different races or genders. More than 70% were male, and 84% were white. As more people begin taking the drug for weight loss, researchers may be able to assemble more data to determine how well it works in broader populations.

This article was first published at Scientific American. © ScientificAmerican.com. All rights reserved. Follow on TikTok and Instagram, X and Facebook.