Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus.
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) expressed in the proximal renal tubules accounts for about 90% of the reabsorption of glucose from tubular fluid. Genetic defects of SGLT2 result in a benign familial renal glucosuria. Pharmacological agents that block SGLT2 are being tested as potential treatment for type 2 diabetes mellitus.


METHODS
A Pubmed search was used to identify all relevant articles on the physiology of SGLTs as well as published preclinical and clinical experimental studies with SGLT2 inhibitors; a reference search of all retrieved articles was also undertaken.


RESULTS
SGLT2 is almost exclusively expressed in the proximal renal tubules. Preclinical studies with selective SLGT2 inhibitors show dose-dependent glucosuria and lowering of blood glucose in models of type 2 diabetes. Preliminary clinical studies of up to 3-month duration show dose-dependent lowering of glycosylated hemoglobin up to 0.9% along with modest weight loss. Side effects include an increase in genital fungal infection compared to placebo, increased urine volume (300-400 ml/24 h), and evidence of volume depletion consistent with mild diuretic effect.


CONCLUSIONS
SGLT2 inhibitors are showing promise as a useful addition to the current therapeutic options in type 2 diabetes mellitus. Results of ongoing phase III clinical trials are awaited and will determine whether the risk-benefit ratio will allow approval of this new class of drug for the management of type 2 diabetes mellitus.
Nair
Sunil
S
Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Longmoore Lane, Liverpool L9 7AL, United Kingdom.
Wilding
John P H
JP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D015195:Drug Design; D005947:Glucose / Q000378:metabolism; D006029:Glycosuria / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose