Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects

Dapagliflozin is a potent and selective inhibitor of sodium-glucose co-transporter type 2 that is being developed for the treatment of type 2 diabetes mellitus. This open- label, randomized, two-period, two-treatment (single doses of 10-mg dapagliflozin fasted or fed), crossover study was conducted to evaluate the effect of a high-fat meal on the pharmacokinetics of dapagliflozin in 14 healthy subjects. Compared to the fasted state, a high-fat meal decreased mean dapagliflozin maximum plasma concentrations (C-max) by 31%, increased the time to C-max (T-max) by 1 h, but did not affect overall dapagliflozin systemic exposure [area under the plasma concentration-time curve (AUC)]. As the cumulative (daily) amount of glucose excreted in the urine induced by dapagliflozin is dependent upon dapagliflozin AUC, the effect of food on dapagliflozin Cmax is unlikely to have a clinically meaningful effect on dapagliflozin's efficacy. On the basis of these findings, dapagliflozin can be administered without regard to meals.