Earlier results from the SELECT trial showed that semaglutide, an injectable GLP-1 medication, reduced the risk of heart attacks, strokes, and other major cardiovascular events by about 20% in people with overweight or obesity and established heart disease who did not have diabetes.

SELECT is the largest study of its kind, funded by Novo Nordisk. It enrolled 17,604 adults aged 45 and older with a BMI of 27 or higher (around the average BMI for UK adults) and established cardiovascular disease. Participants were randomly assigned to receive weekly semaglutide or placebo and were followed for an average of about 40 months.

What wasn’t clear was why the drug protects the heart: is it mainly because people lose weight, or is something else going on?

In a new study published in The Lancet, the same research team examined how changes in weight and waist size related to cardiovascular events. They grouped participants by starting BMI and by how much weight they lost during treatment.

They found that semaglutide provided similar heart benefits in people who were only slightly overweight (BMI around 27) and in those with much higher BMIs.

However, waist size told a slightly different story. A smaller waistline, used as a proxy for visceral fat, explained about one-third of semaglutide’s heart-protective effect after two years.  

John Deanfield, the study’s lead author and a professor at University College London, said the waist-factor finding wasn’t surprising, noting that abdominal fat poses a bigger cardiovascular risk than overall weight.

The remaining two-thirds of semaglutide’s benefit couldn’t be explained by weight or waist changes, suggesting other mechanisms are involved.

A massive new study just revealed that a popular weight-loss medication delivers powerful heart protection even in people who barely slim down.

In fact, adults who were only slightly overweight saw the same cardiovascular benefits as those who lost significant weight.

Dr. Johnson explains why this breakthrough could change how we prevent heart attacks and stroke—regardless of your BMI.

👉 WATCH NOW: The Weight-Loss Drug That Shields Your Heart (Even If You Don’t Lose Weight)

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics the body’s natural GLP-1 hormone, which is released after eating. It helps:

Semaglutide is the active ingredient in Ozempic and Rybelsus, which are approved for type 2 diabetes, and Wegovy, which is approved for obesity and, in some regions, for cardiovascular risk reduction in people with heart disease.

Researchers of the studies believe GLP-1 drugs may support cardiovascular health through several pathways that go beyond fat loss, including:

These broader effects may help explain why semaglutide reduced major cardiovascular events even in people who lost relatively little weight or started with only mild overweight.

Given these findings, the authors argue that semaglutide—and likely other GLP-1 drugs—should be viewed not just as weight-loss or diabetes medications, but as disease-modifying treatments that can influence the course of cardiovascular disease and possibly other age-related conditions. “These findings reframe what we think this medication is doing,” Deanfield said. 

They also highlight that patients don’t need a high BMI or major weight loss to see cardiovascular benefits. This could shift how doctors determine eligibility, potentially extending these medications to people with heart disease and only moderate overweight.

Still, the authors emphasize the need for more research on side effects and long-term safety, especially if these drugs are used broadly or taken for many years.

There’s been a lot of buzz around semaglutide and other GLP-1 drugs because of their powerful weight-loss effects. But these new findings add a new twist: these drugs appear to protect the heart in ways that are only partly explained by slimming down.

For patients with overweight or obesity and heart disease, that’s a benefit worth paying attention to—well beyond the number on the scale.