The medicine behind Ozempic and Wegovy, called semaglutide, could have significant benefits for heart health, reducing the risk of stroke or cardiac arrest even in those who don't lose weight.

The data comes from the largest and longest clinical trial on semaglutide use amongst those without diabetes, called the Semaglutide and Cardiovascular Outcomes (SELECT) trial. This landmark study involved roughly 17,600 overweight or obese adults with pre-existing cardiovascular disease and was funded by the drug manufacturer, Novo Nordisk.

Last year, researchers used that data to show weekly injections of semaglutide, received for over three years, can reduce the risk of stroke, heart attack, or fatal cardiovascular events by almost 20 percent, on average.

Now, a new team, led by cardiologist John Deanfield from University College London, has further shown that those benefits occur regardless of weight loss.

Despite a participant's starting weight or the weight they lost on semaglutide, their risk of an adverse cardiovascular event, such as a heart attack or stroke, still fell by roughly the same amount between 2018 and 2023. Participants in the SELECT trial were 45 years and older, and almost three-quarters were male.

Semaglutide is now famous for its ability to suppress appetite and induce rapid weight loss, but the drug was originally designed to treat diabetes. While clinical trials have shown semaglutide injections can reduce adverse cardiovascular outcomes among those with diabetes, the benefits to patients without insulin issues are less clear.

Some scientists have hypothesized that treating obesity with semaglutide is what improves cardiovascular health, and there may be other benefits.

A recent analysis of the SELECT trial published in Nature Medicine, biomedical researcher Donna Ryan and her colleagues including Deanfield found sustained weight loss – 10 percent on average over four years — in people of all sexes, races, ages, and body sizes.

"This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses," Ryan, from Pennington Biomedical Research Center in the US, says of the results.

"While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management."

But as Deanfield, Ryan and their colleagues point out in their new analysis, not all the health benefits of semaglutide necessarily stem from the treatment of obesity. There may be an unknown mechanism at play that goes beyond a reduction in body fat.

Deanfield presented the new findings at the European Congress on Obesity (ECO) earlier in May, as did Ryan. Together the two studies will no doubt prompt further debate.

Previous studies suggest that once semaglutide injections are stopped, patients typically regain about two-thirds of the weight they lost within a year. The benefits to weight loss in the long run need to be studied further, as do the benefits to cardiovascular risks when semaglutide injections are ceased.

Researchers not involved in either of the two new studies have also cautioned against putting large swathes of the population on semaglutide until more is understood about how the drug works.

With future investigation, the unexpected effects of Ozempic on heart health could change the way scientists understand obesity and cardiovascular disease.

The study led by Ryan has been published in Nature Medicine. The analysis led by Deanfield was presented at ECO ahead of peer review.