INTRODUCTION: Maintenance of glucose homeostasis in healthy individuals involves 
SGLT2 (sodium glucose co-transporter 2)-mediated recovery of glucose from the 
glomerular filtrate which otherwise would be excreted in urine. Clinical studies 
indicate that SGLT2 inhibitors provide an insulin-independent means to reduce 
the hyperglycemia that is the hallmark of type 2 diabetes mellitus (T2DM) with 
minimal risk of hypoglycemia.
AREAS COVERED: The pharmacophore common to the SGLT2 inhibitors currently in 
development is a diarylmethane C-glucoside which is discussed in this review. 
The focus is how this pharmacophore was further modified as inferred from the 
patents publishing from 2009 to 2011. The emphasis is on the strategy that each 
group employed to circumvent the constraints imposed by prior art and how the 
resulting SGLT2 potency and selectivity versus SGLT1 compared with that of the 
lead clinical compound dapagliflozin.
EXPERT OPINION: SGLT2 inhibitors offer a new fundamentally different approach 
for treatment of diabetes. To date, the clinical results suggest that for 
non-renally impaired patients this class of inhibitors could be safely used at 
any stage of T2DM either alone or in combination with other marketed 
antidiabetic medications.