Wegovy has heart health benefits even if weight loss is minimal

The weight-loss drug Wegovy curbs the risk of heart attacks and other cardiovascular problems, even among people who don’t lose much weight on the drug or don’t have severe obesity to start with, a study has shown.

Earlier results from the same trial, called SELECT, suggested that Wegovy – a GLP-1 weight loss drug – may have this effect, but it wasn’t clear if the heart health benefits were just due to weight loss. A study in pigs implied such drugs directly protect the heart, which has now been demonstrated in people.

“The take-home message is that the benefit of these drugs for your heart and arteries is not dependent on your weight loss, which reframes these drugs as being disease-modifying drugs independent of weight benefit,” says John Deanfield at University College London.

Wegovy, along with the type 2 diabetes drug Ozempic, contains the GLP-1 medicine semaglutide. Despite being approved for weight loss and diabetes, such treatments have shown potential for a range of conditions, such as dementia and alcoholism.

The SELECT trial involved comparing semaglutide against a placebo on the cardiovascular risks of 17,604 people, aged 45 and older, who were overweight or obese. None had diabetes, but they all had some form of heart disease. In November 2023, Deanfield and his colleagues reported semaglutide reduced the risk of a heart attack, stroke or other major cardiac event by 20 per cent.

Wondering if this was due to weight loss alone, the researchers have now scrutinised their data across different body mass index (BMI) and weight-loss categories. They have found the people with a starting BMI of 27 – considered mild obesity in some cases – had similar improvements in their heart disease risks after taking semaglutide as those with the highest BMIs, which reached 44, severe obesity.

The team also realised the amount of weight lost – whether in the first 20 weeks or over the trial’s approximate two-year duration – had little bearing on the cardiovascular benefits.

But abdominal fat did appear to play an important role. The team found having a smaller waist at the start of the study was linked to a lower risk of cardiovascular problems, regardless of whether someone was in the semaglutide or placebo groups. But over the course of a couple of years on semaglutide, each 5-centimetre reduction in waist circumference was associated with about a 9 per cent lower risk of cardiovascular events. The team calculated the waistline drop accounted for roughly a third of the drug’s heart-protective benefit; the rest of its effects were less clear.

The results support semaglutide’s potential beyond just weight loss, with the people in the placebo group even experiencing a slightly increased risk of heart problems if they lost weight. This is possibly because this weight loss reflected underlying health issues, says Deanfield.

Further research is required to unpick how semaglutide, and possibly other GLP-1 drugs, have these effects. Improved blood vessel lining and blood pressure might be involved, Deanfield postulates, but an anti-inflammatory effect is also plausible.

“Inflammation turns out to be a very important mechanism for multiple diseases that we’d all like to avoid,” he says. “It looks like this is a common pathway that’s being targeted by these drugs.”

The benefits could also be related to how semaglutide acts on fat tissue around the heart, known as epicardial adipose tissue, says Gianluca Iacobellis at the University of Miami in Florida. “Semaglutide targets epicardial adipose tissue receptors, improves the tissue, and then improves heart function to ultimately reduce the risk of cardiovascular events,” he says.

“The question is: what are the parameters we should use to identify the people who can gain the greatest advantages from the administration of these drugs?” says Stefano Masi at the University of Pisa, Italy. “This is, I think, going to be the challenge for the future.”