The kidneys, like the liver, can contribute to blood glucose concentrations via gluconeogenesis. However, the major and quantitatively more important role of the kidney in glucose homeostasis is the reabsorption of filtered glucose. Glucose reabsorption by the kidney occurs exclusively in the proximal tubule. The sodium-glucose cotransporter 2 (SGLT2), which is found in the proximal tubule of the nephron, is responsible for the bulk of the reabsorption of the glucose in the kidneys. Inhibiting SGLT2 thus increases the glycosuria and reduces plasma glucose concentration, better control of hypertension and weight loss, all without inducing severe hypoglycemia and suitable for combined therapy. Overall, the treatment with SGLT2 inhibitors was safe, without major adverse events but yielded increased risk of mild hypoglycemic events, mostly when superimposed on background insulin therapy, and an increased risk of urinary and genital tract infections. The long-term safety and efficacy of SGLT2 inhibitors are under evaluation.