Therapeutic Research

Abstract

Evidence from large–scale randomized trials demonstrates the limitations of anti –diabetic therapy focused on optimizing glucose control alone, despite the wide array of anti –diabetic treatments currently available. Recent research also suggests that diabetic macroangiopathy（ e.g., cardiovascular disease [CVD]） and microangiopathy（ e.g., chronic kidney disease [CKD]） are both accounted for by the cardio –renal metabolic syndrome （CRS） in which insulin resistance associated with visceral fat accumulation leads to oxidative stress to inflammation to vascular injury resulting in CVD or CKD, thus highlighting the need for a comprehensive therapeutic strategy for the CRS, as well as for targeting the kidneys in anti –diabetic therapy, given their role in the CRS. Indeed, the kidneys have emerged in recent years as a new therapeutic target due to their role in glucose homeostasis, particularly with the advent of sodium– glucose cotransporter 2（SGLT2） inhibitors.Against this background, therefore, the current review discusses the role of the kidneys in glucose homeostasis, the role of SGLT2 as a therapeutic target, and explores the role of SGLT2 inhibitors （inhibition of SGLT2 –mediated glucose reabsorption from the proximal renal tubule） based on the evidence currently available in type 2 diabetes, including their benefits that may vary depending on their pharmacological profiles（e.g., SGLT2 selectivity,pharmacodynamics, plasma protein binding ratio and target tissue distribution）, safety and therapeutic potential beyond glucose lowering for the CRS in type 2 diabetes due to their non –insulin –dependent glucose lowering as well as for CKD as a key factor in the CRS through their inhibitory effects on glomerular hyperfiltration.