Type 2 diabetes is characterized by decreased insulin secretion and sensitivity. 
The available oral anti-diabetic drugs act on many different molecular sites. 
The most used of oral anti-diabetic agents is metformin that activates glucose 
transport vesicles to the cell surface. Others are: the sulphonylureas; agents 
acting on the incretin system; GLP-1 agonists; dipetidylpeptidase-4 inhibitors; 
meglinitide analogues; and the thiazolidinediones. Despite these many drugs 
acting by different mechanisms, glycaemic control often remains elusive. None of 
these drugs have a primary renal mechanism of action on the kidneys, where 
almost all glucose excreted is normally reabsorbed. That is where the inhibitors 
of glucose reuptake (sodium-glucose cotransporter 2, SGLT2) have a unique site 
of action. Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a 
new principle of control in type 2 diabetes that has several advantages with 
some urogenital side-effects, both of which are evaluated in this review. 
Specific approvals include use as monotherapy, when diet and exercise alone do 
not provide adequate glycaemic control in patients for whom the use of metformin 
is considered inappropriate due to intolerance or contraindications, or as 
add-on therapy with other anti-hyperglycaemic medicinal products including 
insulin, when these together with diet and exercise, do not provide adequate 
glycemic control. The basic mechanisms are improved β-cell function and insulin 
sensitivity. When compared with sulphonylureas or other oral antidiabetic 
agents, SGLT2 inhibitors provide greater HbA1c reduction. Urogenital 
side-effects related to the enhanced glycosuria can be troublesome, yet seldom 
lead to discontinuation. On this background, studies are analysed that compare 
SGLT2 inhibitors with other oral antidiabetic agents. Their unique mode of 
action, unloading the excess glycaemic load, contrasts with other oral agents 
that all act to counter the effects of diabetic hyperglycaemia.