Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a 
novel approach for the management of type 2 diabetes mellitus (T2DM). Several 
compounds are already available in many countries (dapagliflozin, canagliflozin, 
empagliflozin and ipragliflozin) and some others are in a late phase of 
development. The available SGLT2 inhibitors share similar pharmacokinetic 
characteristics, with a rapid oral absorption, a long elimination half-life 
allowing once-daily administration, an extensive hepatic metabolism mainly via 
glucuronidation to inactive metabolites, the absence of clinically relevant 
drug-drug interactions and a low renal elimination as parent drug. SGLT2 
co-transporters are responsible for reabsorption of most (90 %) of the glucose 
filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters 
reduces hyperglycaemia by decreasing renal glucose threshold and thereby 
increasing urinary glucose excretion. The amount of glucose excreted in the 
urine depends on both the level of hyperglycaemia and the glomerular filtration 
rate. Results of numerous placebo-controlled randomised clinical trials of 
12-104 weeks duration have shown significant reductions in glycated haemoglobin 
(HbA1c), resulting in a significant increase in the proportion of patients 
reaching HbA1c targets, and a significant lowering of fasting plasma glucose 
when SGLT2 inhibitors were administered as monotherapy or in addition to other 
glucose-lowering therapies including insulin in patients with T2DM. In 
head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar 
glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The 
durability of the glucose-lowering effect of SGLT2 inhibitors appears to be 
better; however, this remains to be more extensively investigated. The risk of 
hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and 
was similarly low as that reported with metformin, pioglitazone or sitagliptin. 
Increased renal glucose elimination also assists weight loss and could help to 
reduce blood pressure. Both effects were very consistent across the trials and 
they represent some advantages for SGLT2 inhibitors when compared with other 
oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors 
declines with increasing severity of renal impairment, and prescribing 
information for each SGLT2 inhibitor should be consulted regarding dosage 
adjustments or restrictions in moderate to severe renal dysfunction. Caution is 
also recommended in the elderly population because of a higher risk of renal 
impairment, orthostatic hypotension and dehydration, even if the absence of 
hypoglycaemia represents an obvious advantage in this population. The overall 
effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and 
will be evaluated in several ongoing prospective placebo-controlled trials with 
cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and 
their potential to influence the course of diabetic nephropathy also deserve 
more attention. SGLT2 inhibitors are generally well-tolerated. The most 
frequently reported adverse events are female genital mycotic infections, while 
urinary tract infections are less commonly observed and generally benign. In 
conclusion, with their unique mechanism of action that is independent of insulin 
secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic 
options available for the management of T2DM at any stage in the natural history 
of the disease. Although SGLT2 inhibitors have already been extensively 
investigated, further studies should even better delineate the best place of 
these new glucose-lowering agents in the already rich armamentarium for the 
management of T2DM.