Obesity, anti-obesity medications, and atrial fibrillation: Recent advances

Obesity and atrial fibrillation (AF) are closely connected conditions that share many metabolic, hemodynamic,and inflammatory pathways. An increasing body mass index is linked to incident AF, AFprogression, and higher recurrence rates after cardioversion or catheter ablation. Notably, obesitycontributes to atrial structural and electrical remodeling through various mechanisms, includingsystemic inflammation, oxidative stress, epicardial adipose tissue buildup, metabolic dysregulation,and changes in calcium handling and connexin expression. These alterations create a proarrhythmicsubstrate that promotes AF initiation and maintenance. Sustained weight loss has been strongly associated with reverse atrial remodeling, improved hemodynamics, decreased AF burden, and lower recurrence rates. In this evolving treatment landscape, anti-obesity pharmacotherapy, particularly glucagon-like peptide-1 receptor agonists (GLP-1RA), has emerged as a promising supplementary strategy. Beyond weight reduction and blood sugar control, these medications have pleiotropic cardiovascular effects, such as anti-inflammatory and antioxidant actions, hemodynamic improvements, decreases in epicardial adipose tissue, and reductions in atrial fibrosis. Several observationalstudies and meta-analyses suggest that GLP-1RA lower the risk of new-onset AF and AF recurrenceafter cardioversion or ablation. However, most available data come from studies in which AF wasa secondary endpoint, involving diverse populations and relatively short follow-up periods. Whileanti-obesity drugs - especially GLP-1RA - show significant potential to influence AF risk andprogression, conclusive evidence requires well-powered, randomized controlled trials with AF asthe primary endpoint, standardized arrhythmia monitoring, and long-term follow-up.