Semaglutide helps your heart even if the scale doesn’t budge, studies show

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

The scientists examined data from a large-scale clinical trial of people with obesity and existing cardiovascular disease. They found that compared to people on placebo, those on semaglutide were less likely to develop heart attacks and other cardiovascular problems — even when the people didn’t lose much weight at all. The results suggest that semaglutide may improve heart health in more ways than one, the researchers and outside experts say.

The findings « highlight that the cardioprotective effects of semaglutide may be independent of obesity and weight loss, » Lawrence Sperling, a preventive cardiologist at Emory University who was not affiliated with the study, told Gizmodo.

It’s good for the heart

Semaglutide and other GLP-1 drugs heralded a new era in the treatment of obesity (and diabetes). But for a while it was unclear whether 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, double-blind study designed to answer this open question, the SELECT study. It involved approximately 17,000 people with obesity and a history of cardiovascular disease who were followed for up to five years. 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 the 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 include cardiovascular disease prevention in high-risk populations.

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

Ultimately, they found no clear link between how much weight someone lost at the start of the study (20 weeks) and their reduced risk of cardiovascular disease. The cardioprotective benefits of semaglutide were also largely the same across 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 compared to someone with the highest level of obesity (BMI above 40).

« This gives us important information that maybe we need to look at the indication for these drugs beyond whether your BMI is more than 27, » Howard Weintraub, a preventive cardiologist and clinical director at the NYU Langone Heart Center for Cardiovascular Disease Prevention, told Gizmodo. Weintraub was one of the lead investigators of the original SELECT study, but was not involved in the new study.

The study found a link between one’s waist circumference at the time of the study and the risk of heart disease. The more a person’s waistline shrunk, for example, the greater the reduction in risk. Waist circumference is another measure of excess body fat. So the reduction of body fat with semaglutide does help explain why it prevents heart disease, but only partially. The researchers estimated that only one-third of the effect of semaglutide in reducing cardiovascular disease could be attributed to trimming the 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 cardiac benefits are largely independent of weight loss, then it would not be useful to limit the prescribing of these drugs based solely on BMI. People taking semaglutide who lose enough weight to no longer qualify as obese may still benefit from continuing the drug because of its heart-protective effects — just as those who don’t lose much weight, either.

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

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

An important question remains to be answered as to exactly how these drugs can improve our heart health. The researchers say part of the drug’s protection likely stems from its anti-inflammatory effects, both on excess body fat and elsewhere. But the drug’s effect on blood sugar control or our blood vessels can also play a role.

Another question is whether these heart-stimulating effects can be seen in people who are not overweight or obese—something Kovacs suspects will soon be put to the test. And it is still important to study whether similar benefits are evident with other GLP-1 drugs, including newer drugs that combine GLP-1 with other compounds.

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

« I don’t think we know everything that GLP-1 agonists do yet, » Weintraub said. « So doctors are going to have to look at this beyond the lens of a TikTok video where kids want to lose a few pounds to look better. That can certainly happen, but I think cosmetic issues and the role of weight loss is only a small part of it. And as a cardiologist, I’m more motivated by the kind of findings we’re seeing here to reduce cardiovascular disease. »