Sodium-Glucose Co-Transporter-2 Inhibitors: An Update on the Evidence for Treatment of Type 2 Diabetes
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are a class of antihyperglycemic agents that can be used to improve glycemic control in the treatment of type 2 diabetes (T2D). SGLT-2 inhibitors block SGLT-2–mediated reabsorption of glucose into circulation. By this mechanism, plasma glucose levels are reduced and glucose is excreted in the urine. Not only do SGLT-2 inhibitors have glucose-lowering effects, but their efficacy in nonglycemic clinical parameters, such as lowering blood pressure and helping in weight loss, may be beneficial for patients with T2D.1
Within the family of sodium-dependent glucose transporters, sodium-glucose co-transporter-1 (SGLT-1) and SGLT-2 transporters are key regulators of glucose reabsorption filtered by the kidney, with expression on 2 regions of the renal proximal convoluted tubule. The majority of glucose reabsorption (90%) is attributed to SGLT-2 within the S1 segment, and the SGLT-1 receptor aids in glucose reabsorption downstream from SGLT-2 in the S3 segment.2 In patients with T2D, an increased filtered load of glucose increases its reabsorption through the SGLT-2 transporters of the kidney. Instead of excreting excess filtered glucose in urine, increased reabsorption causes elevated plasma glucose, thereby leading to the hyperglycemic state.
The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) currently recommend that an SGLT-2 inhibitor may be used as first-line therapy in the management of T2D for patients with glycated hemoglobin (A1C) <7.5%, although stronger Continue reading