Abstract
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have significantly impacted the management of diabetic kidney disease (DKD) and heart failure (HF), providing benefits beyond glycemic control. This review examines the mechanisms through which SGLT2is provide renal and cardiovascular protection and assesses their clinical efficacy. SUMMARY: By inducing glucosuria and natriuresis, SGLT2is alleviate multiple complications induced by chronic hyperglycemia. Moreover, SGLT2is reduce albuminuria, improve tubular function, and modulate erythropoiesis. Additionally, they mitigate inflammation and fibrosis by decreasing oxidative stress and downregulating proinflammatory pathways. Clinical trials have demonstrated significant reductions in renal and cardiovascular events among patients with type 2 diabetes mellitus. A comprehensive review of the literature was conducted through PubMed, highlighting the effects of SGLT2is and the results of major clinical trials involving SGLT2is. KEY MESSAGES: SGLT2is play a crucial role in the management of DKD and HF by addressing multiple pathogenic pathways. Currently, SGLT2is are included in clinical guidelines for DKD and HF management, and their benefits extend to nondiabetic populations. Further research is needed to explore SGLT2is' multifaceted mechanisms and potential applications across diverse patient populations and different disease etiologies.