Sodium-glucose transport: role in diabetes mellitus and potential clinical implications.

PURPOSE OF REVIEW: Current options for glycemic control are less than optimal in terms of efficacy and to reduce complications in the diabetic population. Selective inhibition of SGLT2 in the proximal tubule increases urinary glucose excretion thereby reducing plasma glucose levels, which may present a novel therapeutic approach.

RECENT FINDINGS: SGLT2 inhibitors enhance glucose excretion and improve glycemic control in patients with type 2 diabetes in the absence of clinically relevant hypoglycemia or sustained changes in volume status or glomerular filtration rate. This is associated with lowering of body weight and may reduce systolic blood pressure. The increased glucosuria appears to increase the risk of genital infections but may not increase the risk of urinary tract infections.

SUMMARY: The ability of SGLT2 inhibitors to reduce plasma glucose without inducing increased insulin secretion, clinically relevant hypoglycemia, or weight gain constitutes a major advance. The ability to increase glucose excretion provides a powerful means to treat caloric excess conditions. Important questions remain to be resolved and more clinical research is needed on the long-term effects of SGLT2 inhibition. Potential extrarenal effects need to be explored in order to determine the safety of these compounds. It also remains to be determined whether these drugs lower the toxicity of glucose directly on renal cells, independent of hyperglycemia, which may slow or prevent the progressive nature of diabetic nephropathy.