New oral antidiabetics – pharmaceutical chemical characterization of sodium-glucose cotransporter-2 inhibitors

Selective sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel, innovative class of oral antidiabetic agents for the treatment of type 2 diabetes. The first sodium-glucose transporter (SGLT) inhib­itor to be discovered was a naturally occurring O-glycoside, phlorizin, which is found in a number of plants, including the bark of the apple tree root. Although it can lower blood glucose levels, it is not used for this purpose because it is not a selective inhibitor. The structure of the lead molecule, phlorizin, has been further developed into the SGLT-2 inhibitors that are currently on the market. Their mechanism of action is unique: they selectively and reversibly inhibit the sodium-glucose cotransporter-2 at the level of the renal proximal tubule, causing glucosuria and thus reducing blood glucose levels. Gliflozins can be used as monotherapy or in combination with other antidiabetic agents, but can be also combined with injectable agents (insulin). In this review, we present the history, representatives, production, physicochemical properties, test methods, structure-activity relationships, pharmacological properties and mechanism of action of gliflozins.