The induction of glycosuria using phlorizin, a nonselective inhibitor of renal and intestinal transport was well recognised to lower glucose levels and induce calorie loss in animal models of diabetes. Phlorizin and other similar molecules however were not suitable for clinical use due to adverse effects of non selective inhibition of extra-renal glucose transport system. More recent understanding of the physiology of renal glucose transport system and increased knowledge of rare genetic syndromes of renal glycosuria has resulted in the development of drugs that selectively inhibit the Sodium Glucose Transporter-2 (SGLT2). Among the various agents currently being developed within this drug class, dapagliflozin is the most advanced in clinical development. This article discusses the basic physiology of the SGLT2 transporter system, pharmacokinetics and pharmacodynamic information of dapagliflozin, its efficacy in lowering HbA1c and weight as well as its safety and adverse effects profile. This is discussed based on evidence derived from clinical trials involving a spectrum of patients with diabetes, from drug naïve to individuals already on insulin therapy.
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