Exercise, not liraglutide alone, drives vascular gains after obesity-related weight loss

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Jun 25 2026

A year-long trial suggests that, after major weight loss, movement may do what medication alone cannot: improve key markers of arterial health and inflammation.

Study: Effects of exercise and liraglutide on vascular health and inflammation during weight loss maintenance: a prespecified secondary analysis of the S-LiTE trial. Image Credit: Panumas Yanuthai / Shutterstock

In a recent study published in the journal Nature Metabolism, researchers investigated whether exercise can provide added vascular benefits during weight-loss maintenance in a cohort of adults with obesity who had already achieved significant weight loss during an initial low-calorie diet.

The study comprised a prespecified secondary analysis of data obtained from the S-LiTE trial, wherein 130 per-protocol participants who had already lost an average of 13.7 kg (roughly 12.7% of their body weight) were analyzed after random assignment to placebo, exercise plus placebo, liraglutide (3.0 mg daily), or exercise plus liraglutide.

The study monitored participants' vascular structure, inflammation biomarkers, and endothelial function markers over 52 weeks of the intervention, and found that exercise, alone or combined with liraglutide, significantly reduced participants' carotid artery wall thickness and improved their inflammatory and endothelial biomarker profiles. Liraglutide alone did not statistically improve participants’ measured vascular or inflammatory outcomes, highlighting the importance of physical activity in vascular health during weight-loss maintenance.

Background

Epidemiological and clinical research has identified obesity and physical inactivity as major contributors to today’s global cardiovascular disease (CVD) burden. The outcomes of previous metabolic and cardiovascular trials indicate that excessive body fat triggers a chronic, low-grade inflammatory physiological state characterized by endothelial dysfunction (impairment of the inner lining of blood vessels) and an increased risk of atherosclerosis (the hardening of arteries).

While modern weight-loss medications, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have proven effective in promoting weight loss in people with overweight or obesity, the distinct effects of exercise and GLP-1 RA treatment on vascular structure during weight-loss maintenance remain uncertain, especially in people with obesity without diabetes or established cardiovascular disease.

Despite the growing clinical use of GLP-1 RAs, researchers and clinicians still do not know whether exercise (alone or in combination with these drugs) alters individuals’ vascular health and surrogate markers of cardiovascular risk, including carotid intima-media thickness (cIMT), inflammatory cytokines, and endothelial function biomarkers.

About the study

The present study aimed to address this knowledge gap and inform future clinical research and obesity-management strategies by conducting a prespecified secondary analysis of data from participants in the S-LiTE trial. The S-LiTE trial was a randomized, placebo-controlled study that enrolled adults with obesity in an 8-week low-calorie diet (LCD) intended to reduce baseline body weight by at least 5%.

The present study focused on data from 130 per-protocol S-LiTE participants (obese but without diabetes) who achieved a mean body weight reduction of 13.7 kg (~12.7% of their baseline body weight).

Included participants were randomly assigned to liraglutide (3.0 mg daily), volume-matched placebo, exercise plus placebo, or exercise plus liraglutide for 52 weeks.

Cohorts that included exercise as an intervention notably followed a program designed to align with World Health Organization (WHO) physical activity recommendations, specifically targeting at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly. Data collection involved high-resolution ultrasound to measure participants' cIMT.

Additionally, the study used participants’ blood samples to estimate changes in their inflammatory cytokines (e.g., interleukin-6 [IL-6] and interferon-gamma [IFNγ]) alongside previously established biomarkers of endothelial function (e.g., tissue plasminogen activator [tPA] and adhesion molecules).

Study findings

The study’s analyses revealed statistically significant differences in surrogate vascular and inflammatory outcomes between the treatment groups, underscoring the importance of exercise in facilitating long-term improvements in human vascular structure.

Compared with the placebo-only group, cIMT decreased by 7% (P = 0.01) in the exercise + placebo group and by 6% (P = 0.02) in the exercise + Liraglutide group. The authors noted that the approximate 0.04 mm cIMT change was within a range linked to lower cardiovascular risk in meta-analyses, although whether it translates into clinical benefit remains uncertain.

Evaluations of participants’ inflammatory markers mirrored these outcomes, demonstrating that after 1 year of their respective interventions, IL-6 levels decreased by 26% (P = 0.02) in the exercise + placebo group and by 22% (P = 0.049) in the exercise + Liraglutide group. Additionally, IFNγ levels were found to be reduced by 45% (P = 0.006) in the exercise-only group compared to placebo-only values.

Finally, the analyses of endothelial function markers found that the exercise + Liraglutide group had significant reductions in concentrations of soluble intercellular adhesion molecule-1 (sICAM-1 = -13%; P = 0.007) and soluble vascular cell adhesion molecule-1 (sVCAM-1 = -15%; P = 0.01), alongside a 16% reduction in tPA (P = 0.04).

In contrast, participants treated with liraglutide alone showed no significant improvements in their vascular or inflammatory marker profiles (compared to the placebo group), indicating that the drug’s metabolic benefits did not translate into significant improvements in these measured vascular and inflammatory outcomes in this setting.

However, the findings should be interpreted cautiously because this was a secondary analysis, cIMT is a surrogate endpoint, the analyses were performed in a per-protocol population, no adjustment for multiple comparisons was applied, and the partly supervised exercise program may limit direct generalizability to routine care.

Conclusions

The present study suggests that vascular improvements in adults with obesity are more sensitive to the hemodynamic and anti-inflammatory effects of regular physical activity than to the metabolic changes induced by medication alone during weight-loss maintenance. Its results emphasize that while GLP-1 RAs are effective for weight management in obese populations, they are not substitutes for the vascular benefits associated with regular exercise in this specific clinical context.

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