Losing weight is often the first step people take to improve their health, but keeping that weight off—and making sure it leads to long-term benefits for the heart—requires more than medication.
A new study from the University of Copenhagen shows that regular exercise, not the commonly prescribed weight-loss drug liraglutide, may be key to reducing the risk of heart attacks and strokes after weight loss.
The research, presented at the European Association for the Study of Diabetes (EASD) conference in Vienna, focused on people living with obesity but without diabetes.
It highlights how exercise plays a unique role in protecting the heart and blood vessels, independent of weight loss alone.
Cardiovascular disease is the leading cause of death worldwide, most often triggered by atherosclerosis—a condition in which arteries harden and narrow due to fat deposits and inflammation.
When plaques rupture, they can block blood flow, causing heart attacks and strokes. Obesity increases the risk of this process because it causes chronic low-level inflammation and damages the inner lining of blood vessels.
Both GLP-1 receptor agonists (like liraglutide) and exercise are known to reduce cardiovascular risks in people with obesity. But until now, little was known about their direct effects on the development of atherosclerosis once weight has already been lost.
To investigate, researchers recruited 215 adults aged 18 to 65 with obesity but no diabetes. Participants began with an eight-week low-calorie diet of about 800 calories per day, which led to an average weight loss of 12 percent (around 13 kilograms).
Of these, 195 people who had successfully lost at least 5 percent of their body weight were randomly assigned to one of four groups for a year: exercise alone, liraglutide alone, a combination of exercise and liraglutide, or placebo.
Throughout the year, the scientists tracked several health markers linked to heart disease, including levels of inflammation and the condition of the arteries.
Participants also had ultrasounds of their carotid arteries, which supply blood to the brain, to measure artery wall thickness—a key sign of atherosclerosis.
At the end of the year, all groups had managed to maintain their weight loss. But the big difference came from exercise.
Those who exercised regularly, with or without the drug, showed much lower levels of inflammation—key drivers of atherosclerosis—compared with those who didn’t exercise.
In particular, inflammatory markers like interleukin-6 and interferon-γ dropped by more than 20 percent in exercisers. Exercise also improved blood vessel health and reduced artery wall thickness, signaling a direct benefit against cardiovascular disease.
In contrast, participants taking liraglutide without exercise showed no such improvements in inflammation or artery health, even though they maintained their weight loss.
“Exercise seems to provide protection against the development of atherosclerosis in people who are trying to maintain weight loss,” said lead author Dr. Rasmus Sandsdal. “It plays a role that goes beyond just keeping weight off.”
Professor Signe Sørensen Torekov, the study’s senior author, emphasized the public health importance: “For those trying to maintain weight loss, exercise is crucial in improving long-term health. These findings highlight exercise as a critical part of weight management and heart health.”
While the study had some limitations, including its relatively small sample size, it adds to growing evidence that the body needs more than medication to stay healthy. Exercise not only helps maintain weight but also reduces inflammation, strengthens blood vessels, and lowers the risk of heart disease.
In short, weight-loss drugs may help shed pounds, but exercise is what keeps the heart truly protected.
