The Kidney as a Treatment Target for Type 2 Diabetes

Type 2 diabetes is a complex and progressive disease that affects 8.3% of the U.S. population. Despite the availability of numerous treatment options for type 2 diabetes, the proportion of patients achieving glycemic goals is unacceptably low; therefore, new pharmacotherapies are needed to promote glycemic control in these patients. The kidney normally reabsorbs 99% of filtered glucose and returns it to the circulation. Glucose reabsorption by the kidney is mediated by sodium-glucose co-transporters (SGLTs), mainly SGLT2. SGLT2 inhibition presents an additional option to promote glycemic control in patients with type 2 diabetes. A number of SGLT2 inhibitors have been synthesized and are in various stages of clinical development for the treatment of type 2 diabetes. Results from clinical trials show that these compounds decrease plasma glucose and body weight in treatment-naive patients and in patients receiving metformin or insulin and insulin sensitizers. Overall, SGLT2 inhibitors appear to be generally well tolerated, but in some studies, signs, symptoms, and other reports of genital and urinary tract infections have been more frequent in drug-treated groups than in placebo groups. Additional clinical trials will determine whether this class of compounds with a unique, insulin-independent mechanism of action becomes a treatment option for reducing hyperglycemia in type 2 diabetes.