In the ongoing battle against obesity and its devastating cardiovascular consequences, new research from the University of Copenhagen, Denmark, highlights the paramount importance of regular exercise in maintaining weight loss and protecting against atherosclerosis—one of the foremost precursors to cardiovascular disease. Presented at the prestigious Annual Meeting of The European Association for the Study of Diabetes (EASD) held in Vienna, this groundbreaking study elucidates the contrasting effects of pharmacological intervention using the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide versus sustained physical exercise during weight loss maintenance in adults living with obesity but without diabetes.
Atherosclerosis, the pathological hardening and narrowing of arteries caused by chronic inflammation and fatty deposits, underpins the majority of cardiovascular diseases worldwide. This condition fosters plaque formation in arterial walls, which over time can rupture and precipitate life-threatening heart attacks and strokes. Central to this morbid process is endothelial dysfunction, a state where blood vessels lose their ability to appropriately constrict and dilate, impairing vascular health. Chronic low-grade inflammation, pervasive in individuals with obesity, is a significant catalyst of endothelial dysfunction and subsequent atherosclerosis, making weight loss an essential intervention for mitigating cardiovascular risk.
Both exercise and GLP-1 receptor agonists have individually demonstrated efficacy in mitigating cardiovascular events associated with obesity, such as heart failure and myocardial infarction. However, the nuanced interplay between these interventions and their roles in halting the progression of atherosclerosis during the critical phase of weight maintenance, as opposed to active weight reduction, has remained largely unexplored until now. This study furnishes novel insights by directly comparing the physiological impacts of these two strategies over a prolonged period.
The randomized, placebo-controlled trial enrolled 215 adults aged 18 to 65 years with obesity defined by a body mass index (BMI) ranging from 32 to 43 kg/m². Importantly, none of the participants had diabetes or significant comorbidities at baseline, allowing for a focused assessment of cardiovascular biomarkers uninfluenced by such confounders. Participants initially underwent an 8-week intensive low-calorie diet intervention, consuming just 800 kcal daily under the Cambridge Weight Plan regimen. Of these, 195 individuals who successfully lost a minimum of 5% of their initial body weight—averaging a remarkable 12% reduction, equating to approximately 13.1 kilograms—were randomized into one of four weight-maintenance arms to assess the sustainability and cardiovascular implications of their weight loss.
The four assigned weight maintenance methodologies comprised: (1) a regimen of moderate-to-vigorous physical exercise totaling 150 minutes weekly paired with a placebo; (2) daily administration of liraglutide at a therapeutic dose of 3.0 mg; (3) a combined approach of exercise plus liraglutide; and (4) placebo with no exercise intervention. This design allowed for an intricate dissection of the individual and synergistic effects of behavioral and pharmacological interventions on cardiovascular endpoints during the critical year following weight loss.
To evaluate the multidimensional effects on vascular inflammation and function, researchers meticulously measured circulating levels of key inflammatory cytokines and endothelial biomarkers at three junctures: prior to commencing the low-calorie diet, at the initiation of the weight maintenance phase, and after 12 months of intervention. Inflammatory markers assayed included interleukin-6 (IL-6) and interferon-gamma (IFN-γ), both of which are well-established mediators of systemic inflammation implicated in atherosclerosis progression. Endothelial function was gauged by quantifying intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and tissue plasminogen activator (tPA), all key molecules involved in leukocyte adhesion, vascular inflammation, and thrombosis. In addition, carotid artery intima-media thickness (cIMT) was measured using high-resolution ultrasound as a surrogate marker for subclinical atherosclerosis.
After one year, weight loss was effectively maintained across all groups receiving either exercise, liraglutide, or their combination. Intriguingly, significant differences emerged in inflammatory and endothelial biomarkers exclusively linked to participants engaging in regular physical activity, irrespective of concurrent liraglutide use. Exercisers exhibited marked reductions in systemic inflammatory cytokines, with IL-6 levels averaging 21% lower and IFN-γ concentrations falling by 27% compared to their non-exercising counterparts. This potent anti-inflammatory effect underscores exercise’s capacity to modulate immunological pathways implicated in atherosclerosis beyond weight loss per se.
Moreover, biomarkers reflective of endothelial integrity showed pronounced improvement among physically active individuals. VCAM-1 decreased by 6%, ICAM-1 by 8%, and tPA by 12% on average, indicating enhanced endothelial function and reduced pro-thrombotic activity. Even more compelling, carotid artery ultrasound revealed a significant decrement in cIMT, averaging a 0.024 mm reduction among exercisers. This subtle yet clinically meaningful thinning of arterial walls signifies attenuation in plaque formation and atherosclerotic burden, directly linking exercise to vascular structural benefits.
Contrary to expectations, liraglutide administration did not yield discernible changes in the spectrum of inflammatory or endothelial biomarkers, nor did it affect cIMT measures when compared with placebo or non-exercising groups. While liraglutide remains effective for metabolic control and weight management, these findings suggest that its cardiovascular protection mechanisms may not extend to modulating vascular inflammation or remodeling in the absence of diabetes, at least within the one-year timeframe observed.
Lead investigator Dr. Rasmus Sandsdal emphasized the weight-independent nature of exercise’s cardiovascular protective effects, asserting that while both exercise and GLP-1RA therapy maintained weight loss successfully, exercise uniquely mitigated atherosclerotic risk factors through mechanisms beyond weight reduction alone. This revelation elevates exercise from a complementary adjunct to a critical cornerstone intervention in obesity management for cardiovascular health preservation.
Exercise’s myriad benefits are well documented, encompassing improvements in body composition through favorable shifts in fat and lean mass ratios, elevations in cardiorespiratory fitness evidenced by enhanced maximal oxygen uptake, and systemic metabolic enhancements including insulin sensitivity and lipid profile ameliorations. Collectively, these enhancements forge a robust cardiometabolic defense system, reducing the likelihood of atherosclerotic and cardiovascular complications. The current study reinforces these contributions, establishing a direct link between measurable biochemical and physiological markers of vascular health and habitual exercise during weight maintenance.
Professor Signe Sørensen Torekov, the study’s corresponding author, framed these findings within a broader public health context, highlighting that the spiraling societal and economic burden of obesity-associated cardiovascular disease can only be curbed by embedding regular exercise into weight management paradigms. Her reflections underscored the critical necessity for healthcare providers and policymakers to prioritize physical activity promotion alongside pharmacological approaches in tackling obesity-related cardiovascular risk.
Notwithstanding its compelling insights, the study acknowledges limitations, notably the relatively modest sample size and the supervised nature of exercise interventions within the trial setting. The transition from structured exercise programs under clinical supervision to free-living conditions often challenges adherence and may attenuate real-world efficacy. Consequently, the authors advocate for future studies exploring long-term adherence strategies, potentially involving next-generation GLP-1 receptor agonists with enhanced efficacy profiles and extended treatment durations exceeding one year, to robustly delineate combinatorial impacts on cardiovascular health.
In sum, this rigorously conducted clinical trial delivers persuasive evidence positioning regular exercise as an indispensable agent in modulating vascular inflammation, preserving endothelial function, and mitigating subclinical atherosclerosis in adults living with obesity during the precarious phase of weight maintenance. These findings not only inform clinical practice but also chart a course toward integrated, multidimensional obesity interventions centered on sustainable lifestyle modification for the prevention of cardiovascular disease.
Subject of Research: Cardiovascular effects of exercise versus GLP-1 receptor agonist treatment in weight loss maintenance among adults with obesity
Article Title: Not specified in the source text
News Publication Date: 16-Sep-2025
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Keywords: obesity, weight loss maintenance, exercise, liraglutide, GLP-1 receptor agonist, atherosclerosis, cardiovascular disease, inflammation, endothelial function, intima-media thickness, randomized controlled trial
Tags: atherosclerosis and exercisecardiovascular disease preventioncardiovascular risk factors managementchronic inflammation and obesityendothelial dysfunction and inflammationGLP-1 weight-loss drugs comparisonimportance of physical activityobesity and heart healthpharmacological interventions in obesitypreventing heart attacks and strokesregular exercise benefitsweight loss maintenance strategies
