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

Abstract

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 C(max) 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.

Bioequivalence, Food Effect, and Steady‐State Assessment of Dapagliflozin/Metformin Extended‐release Fixed‐dose Combination Tablets Relative to Single‐component Dapagliflozin and Metformin Extended‐release Tablets in Healthy Subjects

“…This effect was consistent with earlier findings from Kasichayanula et al 13 Single-and multiple-dose PK findings for both dapagliflozin and metformin were similar with either dose of the FDC, and only slight accumulations of dapagliflozin and metformin were observed. This is consistent with previous findings for metformin.…”

The Clinical Efficacy and Safety of Sodium Glucose Cotransporter-2 Inhibitors in Adults with Type 2 Diabetes Mellitus

“…Although twice daily dosing of canagliflozin has been studied, the three agents we reviewed have extended half‐lives that allow for once‐daily dosing. Pharmacokinetics do not appear to be affected by age, body weight, sex, race, administration with food, mild to moderate hepatic function, or mild renal impairment, suggesting that dose adjustments will not be required …”

Dapagliflozin for the treatment of type 2 diabetes

“…The maximum plasma dapagliflozin concentration (C max ) is reached within 2 h, and it is delayed by 30 min and decreased by 39% after a high fat meal. The effect of high-fat diet on dapagliflozin availability is unlikely to be clinically significant because the area under the plasma drug concentration is only slightly (~ 5%) affected by food [15]. Dapagliflozin has a long half-life (13.8 h), which makes it suitable for once-daily dosing [16].…”