SGLT2 inhibitors and GLP-1 receptor agonists show potential for reducing atrial fibrillation risk and recurrence

Atrial fibrillation (AF) is the most common sustained arrhythmia globally, characterized by high morbidity, mortality, and often unsatisfactory clinical outcomes despite current treatments. Traditional drug and interventional therapies have limitations, leaving a significant gap for novel adjunctive strategies. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), initially developed for Type 2 Diabetes Mellitus (T2DM), have demonstrated cardiorenal protective effects beyond glycemic control, making them attractive candidates for AF management due to their broader metabolic and cardiovascular impacts.

This narrative review comprehensively synthesized clinical evidence and mechanistic insights regarding the effects of SGLT2 inhibitors and GLP-1 receptor agonists on atrial fibrillation (AF). The authors examined data on both new-onset AF and post-ablation AF recurrence across common cardiometabolic comorbidities, including Type 2 Diabetes Mellitus (T2DM), heart failure (HF), chronic kidney disease (CKD), and obesity. The review integrated findings from cellular, animal, and human clinical studies to explore the underlying mechanisms of action for these drug classes in AF pathophysiology.

Available evidence suggests that SGLT2 inhibitors are associated with reduced new-onset AF risk in patients with T2DM, HF, and CKD. They also appear to lower post-ablation AF recurrence in high-risk groups. GLP-1 receptor agonists demonstrated beneficial effects on AF in individuals with obesity or heart failure with preserved ejection fraction (HFpEF). Their protective effects are primarily mediated by upstream metabolic regulation and direct influences on atrial electrophysiology, as supported by in vitro, animal, and clinical observations. For instance, mechanisms include improved glucose metabolism, reduced inflammation, and modulation of ion channel activity. However, a significant limitation is that most clinical evidence derives from post hoc analyses and observational studies, with AF rarely serving as a primary endpoint and without systematic measurement. > This leaves the current evidence at a hypothesis-generating stage with limited immediate clinical applicability, highlighting the need for more robust data.