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Semaglutide lowers the risk of heart attacks and other major adverse cardiovascular events, regardless of how much weight a person loses, according to a study published in The Lancet.
In the Novo Nordisk-funded study, published on 22 October 2025, researchers from University College London (UCL) analysed data from the SELECT trial (published in 2023) of 17,604 people from 41 countries aged 45 years and over, who were overweight and had cardiovascular disease (CVD) but did not have diabetes.
As part of the trial, participants were randomly assigned 1:1 to receive either weekly injections of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide or placebo.
Previous analysis of these data by the same research team found that semaglutide reduced heart attacks, strokes and other major cardiac events by 20% in the semaglutide group.
According to the results of the new study, this 20% reduction in major adverse events was observed regardless of participants’ weight at the start of the trial. Participants classed as overweight (i.e. a body mass index [BMI] of 27) — the average BMI for adults in the UK — were found to have similar benefits to those classed as obese (i.e. a BMI of 30 or higher).
The benefits of semaglutide were also observed to be largely independent of how much weight people lost in the first four and a half months of taking semaglutide, the study revealed.
However, the researchers found a link between a reduction in waist circumference and heart benefits, which accounts for one-third of the drug’s protective effect on the heart after two years.
As a result, the researchers said this finding “suggests there are multiple ways the drug benefits the heart, rather than its protective effect on cardiovascular health being due solely to weight loss”, which may include “supporting the health of the lining of blood vessels, reduced inflammation, improved blood pressure control and lower lipid levels“.
Semaglutide simulates the functions of the body’s natural incretin hormones, which help to lower blood sugar levels after a meal. Initially prescribed for adults with type 2 diabetes mellitus, semaglutide is the active ingredient in Wegovy and Ozempic — both manufactured by Novo Nordisk.
Lead author John Deanfield, professor of cardiology at the UCL 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.”
Deanfield added that the results have 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 CVD, restricting [semaglutide’s] use to a limited time only and for those with the highest BMIs doesn’t make sense,” he said.
He explained that the benefits need to be weighed against potential side effects, adding that “investigations of side effects become especially important given the broad range of people this medicine and others like it could help”.
Sonya Babu-Narayan, clinical director at the British Heart Foundation and consultant cardiologist, said: “These intriguing results demonstrate that the benefits of medications like semaglutide on heart health go beyond weight loss alone.”
However, she commented: “More research will be needed to unravel the other mechanisms of action behind the cardiovascular benefits beyond weight and fat loss, such as improvements in blood vessel health, control of blood pressure and blood sugar or inflammation.
“While this is a very large study, which followed patients for a long time, we can’t yet know the potential impact of sustained use of medications like these, especially in cardiovascular patients who are not living with overweight and obesity. Ongoing research must be better representative of all cardiovascular patients, including by involving more women and underrepresented groups, and will be needed to shed light on any side effects that longer-term use may have.
“So-called ‘weight loss drugs’ are becoming important heart medications. But if you have been prescribed them as part of your heart care, it’s important to remember that they are not a substitute for other things that keep our hearts and minds healthier for longer. This includes getting regular physical activity and trying to eat as healthy and nutritious a diet as possible, which will help to maximise your long-term heart health.”
