Unveiling the podocyte-protective effect of sodium-glucose cotransporter-2 inhibitors

The renoprotective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in both diabetic and nondiabetic nephropathy are widely recognized due to results from randomized controlled trials notably the DAPA-CKD and EMPA-KIDNEY trials. Research exploring the mechanisms of renoprotection indicates that SGLT2 inhibitors exert protective effects on podocytes by enhancing autophagy and stabilizing the structure of podocytes and basement membranes. Furthermore, reductions in lipotoxicity, oxidative stress, and inflammation have been confirmed with SGLT2 inhibitor treatment. Recent clinical studies have also begun to explore the effects of SGLT2 inhibitors on nondiabetic podocytopathies, such as focal segmental glomerulosclerosis. In this review, we summarize clinical and laboratory studies that focus on the podocyte-protective effects of SGLT2 inhibitors, exploring the potential for broader applications of this novel therapeutic agent in kidney disease.