Exercise, with or without liraglutide, improves vascular health and reduces inflammation during weight loss maintenance.

Individuals with obesity and inactivity frequently suffer from endothelial dysfunction and accelerated atherosclerosis, significantly increasing cardiovascular risk. Current weight loss strategies often focus on diet and pharmacotherapy, but the long-term impact on vascular health, particularly during weight maintenance, remains a critical gap. GLP-1 receptor agonists like liraglutide are effective for weight management, yet their synergistic role with physical exercise in improving specific vascular and inflammatory biomarkers during sustained weight loss is not fully understood. This study investigates how these interventions influence vascular health and inflammation beyond just weight reduction.

This prespecified secondary analysis of the S-LiTE trial (NCT04122716) involved 130 adults with obesity who first completed a diet-induced weight loss phase. Participants were then randomized to a 52-week weight maintenance program, receiving either regular exercise, liraglutide (dose not specified in abstract), or a combination of both. A control arm (placebo/no exercise) is implied by the randomization, though not explicitly detailed for each group. Primary endpoints for this analysis included carotid intima-media thickness (cIMT) as a measure of vascular health, and systemic pro-inflammatory cytokine levels (interleukin-6, interferon-γ). Endothelial function was assessed via biomarkers sICAM-1, sVCAM-1, and tPA levels.

The study revealed significant improvements in vascular health and inflammatory markers in groups incorporating physical activity. Exercise, whether administered alone or in combination with liraglutide, consistently reduced carotid intima-media thickness (cIMT), a key indicator of subclinical atherosclerosis. Furthermore, both exercise-containing groups showed a reduction in systemic pro-inflammatory cytokine levels, specifically interleukin-6 (IL-6) and interferon-γ (IFN-γ).

Combination treatment, involving both exercise and liraglutide, yielded additional benefits, improving endothelial function biomarkers such as soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and tissue plasminogen activator (tPA).

Crucially, liraglutide monotherapy, without concurrent exercise, did not demonstrate these improvements in vascular health or inflammatory markers. This suggests a primary role for physical activity in mediating these specific benefits, with liraglutide potentially enhancing endothelial function when combined with exercise.