BACKGROUND: The kidney plays an important role in glucose metabolism, and has 
been considered a target for therapeutic intervention. The sodium-glucose 
cotransporter type 2 (SGLT2) mediates most of the glucose reabsorption from the 
proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a 
unique mechanism to lower elevated blood glucose levels in diabetes. The purpose 
of this review is to explore the physiology of SGLT2 and discuss several SGLT2 
inhibitors which have clinical data in patients with type 2 diabetes.
METHODS: We performed a PubMed search using the terms "SGLT2" and "SGLT2 
inhibitor" through April 10, 2012. Published articles, press releases, and 
abstracts presented at national and international meetings were considered.
RESULTS: SGLT2 inhibitors correct a novel pathophysiological defect, have an 
insulin-independent action, are efficacious with glycosylated hemoglobin 
reduction ranging from 0.5% to 1.5%, promote weight loss, have a low incidence 
of hypoglycemia, complement the action of other antidiabetic agents, and can be 
used at any stage of diabetes. They are generally well tolerated. However, due 
to side effects, such as repeated urinary tract and genital infections, 
increased hematocrit, and decreased blood pressure, appropriate patient 
selection for drug initiation and close monitoring after initiation will be 
important. Results of ongoing clinical studies of the effect of SGLT2 inhibitors 
on diabetic complications and cardiovascular safety are crucial to determine the 
risk-benefit ratio. A recent decision by the Committee for Medicinal Products 
for Human Use of the European Medicines Agency has recommended approval of 
dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and 
exercise, in combination with other glucose-lowering medicinal products, 
including insulin, and as a monotherapy for metformin-intolerant patients. 
Clinical research also remains to be carried out on the long-term effects of 
glucosuria and other potential effects of SGLT2 inhibitors, especially in view 
of the observed increase in the incidence of bladder and breast cancer. SGLT2 
inhibitors represent a promising approach for the treatment of diabetes, and 
could potentially be an addition to existing therapies.