Potential Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors in Regulating Cardiac and Renal Fibrosis
Abstract
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of agents initially developed for glycemic control in type 2 diabetes mellitus. Beyond their glucose-lowering effects, accumulating clinical evidence has demonstrated significant cardiorenal protective benefits in patients with chronic kidney disease (CKD), irrespective of diabetic status. Cardiac and renal fibrosis are central pathological processes contributing to CKD progression and cardiovascular dysfunction. However, the mechanisms underlying the anti-fibrotic effects of SGLT2 inhibitors remain incompletely understood.
Summary: This review summarizes current experimental and clinical evidence regarding the role of SGLT2 inhibitors in modulating cardiac and renal fibrosis. We discuss their potential mechanisms, including hemodynamic regulation, metabolic reprogramming, attenuation of oxidative stress and inflammation, inhibition of pro-fibrotic signaling pathways, and modulation of cellular crosstalk within the cardiorenal axis. Emerging insights from molecular and translational studies are integrated to clarify how SGLT2 inhibitors may exert anti-fibrotic effects beyond glycemic control.
Key messages: SGLT2 inhibitors confer cardiorenal protection that extends beyond glucose lowering and involves multifaceted anti-fibrotic mechanisms. Understanding these molecular and cellular pathways may provide new therapeutic perspectives for targeting fibrosis in CKD and cardiovascular disease.
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