Abstract
Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, ion channel dysregulation, and autonomic imbalance, thereby promoting AF initiation and progression. Conventional rhythm control strategies remain less effective in diabetic individuals, underscoring the need for innovative, substrate-targeted interventions. In this context, sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising agents with pleiotropic antiarrhythmic properties, modulating fibrosis, inflammation, and mitochondrial integrity. Moreover, advances in anti-inflammatory, antifibrotic, and ion channel-modulating therapeutics, coupled with novel mitochondrial-targeted strategies, are reshaping the therapeutic landscape. Multi-omics approaches are further refining our understanding of diabetes-associated AF, facilitating precision medicine and biomarker-guided interventions. This review delineates the molecular nexus linking diabetes and AF, critically appraises emerging rhythm control strategies, and outlines translational avenues poised to advance individualized management in this high-risk population.