A large international study has found that the weight-loss drug Semaglutide significantly reduces the risk of heart attack or stroke, regardless of how many kilograms a person loses. The findings, published in The Lancet, suggest that the drug’s protective effect on the heart is not solely tied to the amount of weight shed.
Researchers from University College London (UCL) and multiple collaborating institutions looked at data from the “SELECT” trial, which enrolled more than 17,000 participants aged 45 and over across 41 countries. These individuals were overweight or obese and had at least one cardiovascular risk factor, yet did not have established cardiovascular disease at the time of enrolment.
Participants were randomised to receive either weekly injections of semaglutide or a placebo. Previously, the trial had found the drug reduced major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal heart attack and non-fatal stroke, by roughly 20 %.In the latest analysis, researchers found this benefit held true irrespective of how much weight individuals lost in the first four months of treatment.
The team also discovered that while overall weight loss did not meaningfully predict the heart benefit, a reduction in waist circumference, a marker for abdominal fat, was linked to better outcomes. They estimated that about one-third of the cardiovascular risk reduction was mediated through the reduction in waist size, but about two-thirds of the benefit remained unexplained by this measure.
Lead author Professor John Deanfield, from UCL’s Institute of Cardiovascular Science, noted that the findings “reframe what we think this medication is doing”. He explained that while the drug is labelled as a weight-loss injection, “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.”
Deanfield went on to say that the data implied that doctors should consider using semaglutide not only in people with very high body-mass-index (BMI) readings, but potentially in a wider set of people who have cardiovascular risk, even if they are only mildly overweight. He added that restricting the drug’s use to those with the highest BMIs or limiting it to short-term use “doesn’t make sense” if the aim is to reduce cardiovascular disease.
Experts caution, however, that while the cardiovascular benefits appear clear, the use of semaglutide should still be balanced against possible side effects and cost issues. Deanfield emphasised the importance of investigating side-effects, especially because the scope of use could be far broader than in earlier trials.
From a public-health perspective, the study suggests a shift in thinking: instead of viewing weight-loss medications purely as tools for shrinking body size, they might also serve as direct interventions for cardiovascular risk reduction. For people who are overweight or have obesity, but do not yet have heart disease, this represents a potential new strategy to help prevent heart attacks and strokes.
Still, researchers and clinicians say lifestyle measures, such as improving diet, increasing physical activity and quitting smoking, continue to be foundational, and should accompany any pharmacological treatment. While semaglutide offers promise beyond weight loss, it does not replace traditional cardiovascular risk-factor management.
Looking ahead, the team behind the trial says further work is needed to understand exactly how semaglutide delivers its heart-protective effect, beyond the contribution of waist-size reduction. Additional research in varying populations, longer follow-up periods and real-world settings will help clarify how to integrate the drug into broader clinical practice.
In summary, the new findings strengthen the case for semaglutide as a tool not only for weight management but also for cardiovascular prevention, showing that heart-attack and stroke risk can be lowered even when weight loss is modest. The implication is clear: in populations at risk, the medication might work in ways beyond simply shrinking the scale number.
Source
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01375-3/fulltext
