Exercise After Weight Loss: The True Heart Protector Beyond Weight-Loss Drugs

Maintaining weight loss through regular exercise, rather than relying on the weight-loss drug liraglutide (a GLP-1 receptor agonist), appears to better protect adults with obesity from developing atherosclerosis — the dangerous artery-hardening process that triggers heart attacks and strokes. This research, conducted in adults with obesity but without diabetes, comes from the University of Copenhagen, Denmark, and was presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Vienna.

“Our findings reveal that regular exercise is crucial to helping people living with obesity get the full cardiovascular benefits after a substantial weight loss,” said lead author Dr Rasmus Sandsdal from the University of Copenhagen, Denmark.

Why is This Finding Important for Heart Health?

Cardiovascular disease is the leading cause of death worldwide and often originates in atherosclerosis, a chronic condition in which inflammation and fat deposits cause arteries to harden and narrow. Over time, plaques can rupture, causing serious complications such as heart attacks and strokes.

Obesity causes chronic low-grade inflammation, which can lead to endothelial dysfunction (a condition in which the blood vessels become unable to contract and relax adequately) and the development of atherosclerosis.

Both exercise and GLP-1RAs have been shown to reduce the obesity-associated risk of cardiovascular events like heart failure and heart attacks, but little is known about their impact on the development of atherosclerosis during weight loss maintenance.

How was The Trial Conducted?

To explore this further, Danish researchers conducted a randomized placebo-controlled trial involving 215 adults (aged 18-65 years; 63% female) living with obesity (BMI 32-43 kg/m²) who did not have diabetes or other serious chronic disease at the start of the trial.

Initially, participants were asked to adhere to a low-calorie diet of 800 kcal/day (Cambridge Weight Plan) for 8 weeks. The 195 participants who had lost at least 5% of their body weight (average reduction of 12%/13.1 kg) were randomly assigned for 1 year to one of four weight maintenance strategies:

• Exercise (150 min/week) + placebo
• Liraglutide (3.0 mg/day)
• Combination (exercise + liraglutide)
• Placebo

Blood levels of inflammatory biomarkers (interleukin-6 [IL-6], interferon-γ [IFN-γ]) and biomarkers of endothelial function (intercellular adhesion molecule [ICAM-1], vascular adhesion molecule [VCAM-1], tissue plasminogen activator [tPA]) were measured at three points: the start of the low-calorie diet, the start of the weight maintenance period, and after one year. Participants also had an ultrasound of the carotid artery to measure intima-media thickness [cIMT].

What were The Key Findings?

After the 1-year weight maintenance period, both exercising participants and those undergoing liraglutide treatment maintained weight loss.

Nevertheless, the study found that participants who followed an exercise program (with or without liraglutide) had lower levels of inflammatory biomarkers compared with non-exercising participants (average IL-6 level 21% lower, IFN-γ level 27% lower).

Exercising also had a favorable impact on biomarkers of endothelial function (average 6% drop in VCAM-1, 8% drop in ICAM-1, 12% decrease in tPA) compared to non-exercising participants, and reduced carotid artery thickness (average -0.024 mm).

Interestingly, no differences were noted in inflammatory biomarkers, endothelial function markers, or carotid artery thickness between participants treated with liraglutide and those not taking the drug.

What Does This Mean For Patients?

“Regular exercise seems to confer a protective effect against the development of atherosclerosis in people trying to maintain weight loss. Since both exercise and GLP-1RA treatment were successful at keeping weight off, it seems that exercise plays an important role in mitigating cardiovascular risk factors in a weight-independent manner,” said Dr Sandsdal.

Exercise benefits health in numerous ways, including improving body composition and increasing cardiorespiratory fitness. These benefits collectively contribute to improved cardiometabolic health.

“The most important message from our findings is that, for those trying to maintain weight loss, exercise is crucial in improving long-term health,” said corresponding author Professor Signe Sørensen Torekov from the University of Copenhagen. “Given the substantial societal and economic costs of obesity-related cardiovascular disease, these findings underscore regular exercise as a critical component of weight management and heart health.”

What are The Study Limitations?

The study had some limitations, including the small sample size and that performing the structured exercise program outside the support of this trial, in free-living conditions, might reduce individual adherence. The researchers note that future research should investigate the combined effects of adherent exercise and newer GLP-1RAs for treatment periods longer than one year.

Source-University of Copenhagen / EASD 2025