The weight-loss drug semaglutide cuts the risk of heart attack or stroke regardless of how many kilograms people lose, the largest study of its kind has found.
However, shrinking waist size – a sign of less belly fat – was linked to better heart outcomes, according to the research.
The findings, published in the Lancet, suggest drugs could have wider benefits for patients beyond weight loss so should not be restricted to the most obese patients.
Researchers set out to examine the additional benefits of semaglutide, which is the main ingredient of the weight-loss drug Wegovy.
The select trial, led by University College London (UCL), looked at whether or not people taking the drug went on to suffer a “major adverse cardiac event” – including heart disease deaths, heart attacks or strokes.
They examined data on 17,604 people aged 45 and over who were either overweight or obese.
Half of the people taking part in the study – which took place across 41 countries – were given weekly injections of semaglutide. The other half were given a dummy drug, known as a placebo.
Previous analysis of the data found that semaglutide reduced the risk of major adverse cardiac events by 20%. Researchers have now found the benefit was apparent regardless of how much weight people lost while taking the drug.
Academics said the findings suggested there were multiple ways the drug could benefit the heart, rather than the protective effect achieved solely by weight loss alone.
They found that even people who were only mildly overweight, with a body mass index (BMI) score of 27 – the average BMI score for UK adults – experienced similar benefits to those who had the highest BMI scores.
The benefits were also largely independent of how much weight people lost in the first four months of treatment.
However, researchers did notice a difference between shrinking waistlines, measured by waist circumference, and heart benefits.
Writing in the Lancet, they said that an “estimated 33% of the observed benefit on major adverse cardiovascular events was mediated through waist circumference reduction”.
The lead author, Prof John Deanfield, of UCL’s Institute of Cardiovascular Science, said: “Abdominal fat is more dangerous for our cardiovascular health than overall weight and therefore it is not surprising to see a link between reduction in waist size and cardiovascular benefit.
“However, this still leaves two-thirds of the heart benefits of semaglutide unexplained. These findings reframe what we think this medication is doing.
“It is labelled as a weight-loss jab but its benefits for the heart are not directly related to the amount of weight lost – in fact, it is a drug that directly affects heart disease and other diseases of ageing.”
He added: “This work has implications for how semaglutide is used in clinical practice.
“You don’t have to lose a lot of weight and you don’t need a high BMI to gain cardiovascular benefit. If your aim is to reduce cardiovascular disease, restricting its use to a limited time only and for those with the highest BMIs doesn’t make sense.
“At the same time, the benefits need to be weighed against potential side-effects. Investigations of side-effects become especially important given the broad range of people this medicine and others like it could help.”