Sodium-glucose co-transporters (SGLT2) are mainly expressed in the kidneys and 
are responsible for the renal handling of glucose load. SGLT2 inhibitors 
represent the latest oral agents for diabetes treatment. Their unique mechanism 
of action, which practically spares the insulin secretion or insulin 
utilization, differentiates the SGLT2 inhibitors from any existing antidiabetic 
agent. Thus, it is hypothesized that SGLT2 inhibitors can be effectively (and 
probably safely) combined with any existing antidiabetic agent (including 
insulin), either as monotherapy, or in dual or triple combinations. All these 
hypotheses are currently tested in many clinical trials. Currently 
dapagliflozin, one of the three most advanced SGLT2 inhibitors in the 
development (along with canagliflozin and empagliflozin), is already in the 
market in few European countries and canagliflozin has been approved from the 
Food and Drug Administration (FDA) in US. The evidence so far shows that SGLT2 
inhibitors are equally effective to established antidiabetic agents such as 
metformin or sulfonylureas in their ability to lower HbA1c. On the other hand, 
SGLT2 inhibitors increase the possibility of genitourinary infections in type 2 
diabetic individuals. Their potency in different populations and with different 
background therapy, but more importantly their short and long term safety 
remains to be seen.