Sodium–glucose cotransporter-2 inhibitors for diabetic kidney disease: Targeting Warburg effects in proximal tubular cells

Inhibitors of sodium–glucose cotransporter 2 (SGLT2) have undoubtedly shifted the paradigm for diabetes medicine and research and, especially, diabetic kidney disease (DKD). The pharmacological action of SGLT2 inhibitors is simply the release of glucose into urine; however, precisely how SGLT2 inhibitors contribute to the health of those with diabetes has still not been completely elucidated. Towards this end, the present review provides a novel insight into the action of SGLT2 inhibitors by highlighting a neglected fuel-burning system found in proximal tubular cells—‘glycolysis’. In addition, exploring the details of the molecular mechanisms and clinical biomarkers of the organ protection conferred by SGLT2 inhibitors is now required to prepare for the next stage of clinical diabetes medicine—the ‘post-SGLT2 inhibitor era’.