Molecular Synergy of SGLT2 Inhibitors and GLP-1R Agonists Targets Atrial Cardio-Metabolic Inflammation

Cardio-metabolic disease is increasingly recognized as a significant contributor to atrial remodeling and atrial fibrillation (AF). Inflammation and oxidative stress play central roles in this process, now considered key components of atrial cardiomyopathy (AtCM). While SGLT2 inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists have transformed the management of heart failure with preserved ejection fraction through their anti-inflammatory and antioxidant effects, their direct contribution to atrial substrate biology and the impact of their combined modulation on atrial remodeling remain areas of active investigation.

This review synthesizes current understanding of molecular synergy and inflammatory activation in atrial cardio-metabolic cardiomyopathy, drawing from preclinical and clinical observations. It highlights studies, such as one by Fakih et al., which analyzed right atrial appendage samples from 80 patients undergoing cardiac surgery (18 with AF, 62 in sinus rhythm). This cited work also utilized cultured human coronary artery endothelial cells, a human cardiomyocyte line (AC16 cells), and peripheral blood mononuclear cells to investigate TNFα-expression and the role of SGLT2 and GLP-1R signaling in atrial inflammation and oxidative stress.