Weight-loss medications can help people lose or maintain weight, but a new study suggests they may not replace the broader health benefits of regular movement.
The study, published in Nature Metabolism, followed 130 adults with severe obesity after they completed an eight-week low-calorie diet and lost an average of 13.7 kilograms, or about 13% of their body weight. In a prespecified secondary analysis of a randomized clinical trial, researchers found that participants assigned to exercise, either alone or with liraglutide, showed improvements in certain blood-vessel and inflammation markers after one year. Those assigned to liraglutide alone maintained weight loss but did not show the same vascular improvements.
The trial studied liraglutide, an earlier GLP-1 medication, not newer drugs such as semaglutide or tirzepatide. Novo Nordisk provided the study medication injection pens, and the work received funding from the Novo Nordisk Foundation, among other sources. Several authors also disclosed financial ties to Novo Nordisk or other pharmaceutical companies.
Researchers divided participants into four groups after their initial weight loss: exercise only, liraglutide only, exercise plus liraglutide or placebo. The exercise groups trained for about two and a half hours per week on average, mainly through spinning and circuit training. Their activity was tracked with heart-rate monitors.
After one year, the researchers measured carotid artery wall thickness, a marker associated with cardiovascular risk. Thicker artery walls can signal a higher risk of atherosclerosis and related cardiovascular problems, though this measure is not the same as tracking actual heart attacks, strokes or blood clots.
Participants in the exercise groups had a 6% to 7% reduction in carotid artery wall thickness. The liraglutide-only and placebo groups did not show that improvement. Exercise was also linked with lower levels of inflammatory markers, including IL-6 and IFN-gamma.
“Medication can help maintain weight loss, but exercise provides additional health benefits that we do not see with medication alone,” said Rasmus Sandsdal, medical doctor, PhD student at the Department of Biomedical Sciences and first author of the study.
The combination of exercise and liraglutide led to additional weight loss and improved several measures of vascular function. That makes the study less a medication-versus-exercise story and more a reminder that obesity care often involves different tools doing different things.
The findings are especially timely as GLP-1 medications become more widely used for weight management. These medications can play an important role in care, but weight loss alone may not capture every change that matters for long-term health.
“The participants were in their mid-40s and had not yet developed diabetes or heart disease, so it’s encouraging that even a modest amount of exercise can improve key risk factors for cardiovascular disease," Sandsdal said.
The study has limits. It included a relatively small group of adults with severe obesity who had already completed a structured low-calorie diet and achieved significant weight loss before the one-year intervention began. The results also apply specifically to liraglutide and cannot be assumed to apply in the same way to newer GLP-1 medications.
Still, the study points to an important distinction: maintaining weight loss and improving cardiovascular risk markers may not always be the same thing. For people using weight-loss medication, the findings support the idea that physical activity can remain a meaningful part of care, not as punishment or proof of willpower, but as a separate contributor to heart and blood-vessel health.
The study was funded by grants from the Novo Nordisk Foundation and Helsefonden. Cambridge Weight Plan supplied diet-replacement products, and Novo Nordisk provided the study medication injection pens. Several researchers also received support from programs funded by the Novo Nordisk Foundation, the Danish Heart Foundation and the European Union’s Horizon Europe program.
Several authors also disclosed ties to Novo Nordisk or other pharmaceutical companies, including advisory board roles, lecture fees, research grants, travel support, employment after study data collection, family employment and stock ownership.