Treatment of type 2 diabetes (T2DM) continues to present challenges, with 
significant proportion of patients failing to achieve and maintain glycemic 
targets. Despite the availability of many oral antidiabetic agents, therapeutic 
efficacy is offset by side effects such as weight gain and hypoglycemia. 
Therefore, the search for novel therapeutic agents with an improved benefit-risk 
profile continues. Recent research has focused on the kidney as a potential 
therapeutic target, especially because maximal renal glucose reabsorption is 
increased in T2DM. Under normal physiological conditions, nearly all filtered 
glucose is reabsorbed in the proximal tubule of the nephron, principally via the 
sodium-glucose cotransporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral 
antidiabetics, which reduce hyperglycemia by increasing urinary glucose 
excretion independently of insulin secretion or action. Clinical results are 
promising with significant lowering of HbA1c without increased risk of 
hypoglycemia, reduction of body weight and reduction of systolic blood pressure. 
Dapagliflozin is the first highly selective SGLT2-inhibitor approved by the 
European Medecine Agency. Canagliflozin and empagliflozin are undergoing phase 
III trials. Actual safety issues are an increased risk for genital- and urinary 
tract infections and a possible increased risk for bladder and breast cancer. 
This led to refusal of dapagliflozin by the Food and Drug Administration (FDA). 
A large randomized control trial is therefore warranted by the FDA. This review 
provides an overview of the current evidence available so far on the therapeutic 
potential of the SGLT2-inhibitors for the treatment of T2DM.