The sodium-glucose cotransporter-2 (SGLT2) inhibitors are diabetic agents that act by inhibiting the reabsorption of glucose in the proximal renal tubule, resulting in loss of glucose in the urine and reduction in serum levels. SGLT2 is the major enzyme responsible for glucose reabsorption in the kidney and its inhibition causes a reduction in the threshold for glucose loss in urine. The excess loss of glucose causes a loss of calories, reduction in serum glucose and mild osmotic diuresis. The SGLT2 inhibitors also cause a modest weight loss and slight decrease in blood pressure, both of which may contribute to their beneficial effects. Five specific SGLT2 inhibitors, bexagliflozin, canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, have been shown to result in improvements in glycemic control in type 2 diabetes and introduced into clinical use. Canagliflozin, dapagliflozin and empagliflozin have also been shown to decrease cardiovascular complications and mortality in patients with type 2 diabetes and cardiovascular disease, and to reduce the risk of hospitalization for heart failure and development of end stage renal disease in patients with type 2 diabetes and chronic kidney disease. In prelicensure studies, none of the five agents was reported to be associated with increases in serum aminotransferase or alkaline phosphatase levels and, since licensure, there have been only very rare, isolated, and not completely convincing reports of clinically apparent liver injury associated with their use.