Sergliflozin, the active entity of sergliflozin etabonate, is a selective inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The pharmacokinetics and pharmacodynamics of sergliflozin were evaluated following single oral dose administration of sergliflozin etabonate (5-500 mg) in healthy volunteers (n = 22) and patients with type 2 diabetes mellitus (n = 8). The prodrug was rapidly and extensively converted to sergliflozin; the latter displayed linear kinetics, reached maximum plasma concentrations at approximately 30 to 45 minutes postdose (t(max)), and had a plasma elimination half-life (t(1/2)) of approximately 0.5 to 1 hour. Both prodrug and active entity showed low glomerular filtration and/or extensive renal tubular reabsorption, with <0.5% of the administered dose being recovered in the urine. In both populations, sergliflozin etabonate produced a dose-related glucosuria under fasting conditions and following glucose loading but did not appreciably affect urinary electrolyte excretion or fluid balance. The magnitude and duration of the glucosuric effect closely paralleled plasma sergliflozin concentrations. Sergliflozin did not significantly affect fasting plasma glucose levels but produced transient attenuation of the plasma glucose AUC following glucose challenge. Single doses of sergliflozin etabonate 5 to 500 mg were well tolerated, and there were no clinically significant adverse laboratory findings.