Semaglutide Helps Your Heart Even If the Scale Doesn’t Budge, Study Shows

The benefits of semaglutide, the active ingredient in popular drugs Ozempic and Wegovy, aren’t just limited to treating obesity. New research shows that semaglutide can protect people’s hearts regardless of how many pounds they lose while taking it.

Scientists examined data from a large-scale clinical trial of people with obesity and pre-existing cardiovascular disease. Compared to people on placebo, they found, those on semaglutide were less likely to develop heart attacks and other cardiovascular problems—even when people hadn’t lost much weight at all. The results indicate that semaglutide can improve heart health in more than one way, the researchers and outside experts say.

The findings “highlight that the cardioprotective effects of semaglutide may be independent of adiposity and weight loss,†Laurence Sperling, a preventive cardiologist at Emory University not affiliated with the study, told Gizmodo.

Good for the heart

Semaglutide and other GLP-1 drugs have heralded a new era of obesity (and diabetes) treatment. But for a time, it was unclear if these drugs would also improve people’s cardiovascular health, and to what extent.

Novo Nordisk (the makers of Ozempic and Wegovy) funded a large, randomized, controlled, and double-blinded study designed to answer that open question—the SELECT trial. It involved roughly 17,000 people with obesity and a history of cardiovascular disease, who were followed for up to five years. The primary results from the SELECT trial, published almost two years ago, showed that high-dose semaglutide (the version approved as Wegovy for treating obesity) reduced people’s risk of heart attacks and other major cardiovascular events by 20% during the study period. Based on these findings, the Food and Drug Administration expanded its approval of Wegovy to also cover the prevention of cardiovascular disease in high-risk groups.

Since obesity is known to increase the risk of heart disease, it’s easy to assume that semaglutide’s heart benefits are mostly tied to helping people lose weight. But some evidence has already suggested it’s more complicated than that. In this new research, some of the researchers who conducted the SELECT trial took a closer look at their data.

They ultimately found no clear relationship between how much weight someone had lost early into the study (20 weeks in) and their reduced risk of cardiovascular disease. The heart-protective benefits of semaglutide were also largely the same across different baseline weight groups. In other words, someone who was overweight (a body mass index between 27 and 30) at the start of the study tended to see a similar reduction in heart disease risk as compared to someone with the highest level of obesity (a BMI over 40).

“This gives us important information that maybe we should be looking at the indication for these drugs beyond just whether your BMI is more than 27,†Howard Weintraub, preventive cardiologist and clinical director at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, told Gizmodo. Weintraub was one of the lead researchers of the original SELECT trial but wasn’t involved in the new research.

The study did see an association between someone’s waist circumference throughout the study and heart disease risk. The more a person’s waist shrunk, for instance, the greater reduction in risk they had. Waist circumference is another measure of excess body fat. So semaglutide’s slimming of body fat does seem to help explain why it prevents heart disease—but only partly. The researchers estimated that just a third of semaglutide’s effect on lowering cardiovascular disease could be accounted for by a trimming waistline.

The team’s findings were published Tuesday in The Lancet.

Beyond weight loss

The authors say these findings could have far-reaching implications for how semaglutide and similar GLP-1 drugs should be used. If its heart benefits are largely independent of weight loss, then it wouldn’t be helpful to limit the prescribing of these drugs based solely on BMI. People taking semaglutide who lose enough weight to no longer qualify as obese might still benefit from continuing the drug for its heart-protective effects—just as those who don’t lose much weight may, too.

It’s even possible that GLP-1 therapy could one day be reframed as a standalone treatment for heart disease, regardless of BMI. Richard Kovacs, the interim chief of cardiovascular medicine at Indiana University’s School of Medicine, who is not involved with the study, notes that these findings could shape future guidelines in how doctors manage cardiovascular disease.

“This is a potential guideline changer because of its robust effect here. This is a well-run, large trial that we’re all familiar with. It’s an important analysis of it,†Kovacs, who is also the chief medical officer for the American College of Cardiology, told Gizmodo. At the same time, he adds, it would probably still take more data from at least one other large randomized trial for such a change to happen easily.

One important question left to answer is exactly how these drugs can improve our heart health. The researchers argue that some of the drug’s protection likely stems from its anti-inflammatory effects, both on excess body fat and elsewhere. But the drug’s influence on blood sugar control or our blood vessels could also be playing a part.

Yet another question is whether these heart-bolstering effects can be seen in people who aren’t overweight or obese—something that Kovacs suspects will be put to the test soon enough. And it’s still important to study whether similar benefits are apparent with other GLP-1 medications, including newer drugs that are combining GLP-1s with other compounds.

For now, this research is continuing to demonstrate that there’s still so much left to learn about these already game-changing drugs.

“I don’t think we know everything that the GLP-1 agonists do yet,†Weintraub said. “So doctors will need to look at this beyond the prism of a TikTok video, where kids are looking to lose a couple of pounds to look better. That may certainly happen, but I think the cosmetic issues and the role of weight loss are just a small part of it. And as a cardiologist, I’m more motivated by the sort of findings we’re seeing here in reducing cardiovascular disease.â€