Introduction: Type 2 diabetes mellitus (T2DM) is a growing and serious global health problem. Pharmacological inhibition of the sodium-glucose cotransporter-2 (SGLT2; SLC5A2) increases urinary glucose excretion, decreasing plasma glucose levels in an insulin-independent manner. Agents that inhibit SGLT2 have recently become available for clinical therapy of T2DM.
Areas covered: The patent claims a new class of SGLT2 inhibitors: derivatives of dioxa-bicyclo[3.2.1]octane-2,3,4-triol (including ertugliflozin; PF-04971729). The invention describes the design, synthesis and pharmacological tests related to ertugliflozin, which could ultimately lead to efficacious therapy for T2DM alone or in combination with other anti-diabetic agents.
Expert opinion: Ertugliflozin is likely to be of great clinical significance in the near future. Continued analysis of ertugliflozin derivatives to now validate safe and efficacious treatment of T2DM in a larger number of clinical subjects over an extended period is needed to further support clinical utility. Identification, and discussion, of likely contra-indications is also needed.
Keywords: PF-04971729; clinical therapy; diabetes; dioxa-bicyclo[3.2.1]octane-2,3,4-triol derivatives; ertugliflozin; inhibitors; sodium–glucose linked co-transporter; type 2 diabetes mellitus.