Empagliflozin (BI 10773), a Potent and Selective SGLT2 Inhibitor, Induces Dose‐Dependent Glucosuria in Healthy Subjects

Abstract

Empagliflozin is an orally available, selective inhibitor of sodium glucose cotransporter 2. In this study, single oral doses of empagliflozin from 0.5 to 800 mg were not associated with any clinically significant safety concerns in healthy male volunteers. The incidence of adverse events (AEs) was similar in subjects receiving placebo (22.2%) or empagliflozin (25.0%) in the single rising dose part of the study and after 50 mg empagliflozin under fed (28.6%) or fasted (28.6%) conditions. The most frequent AE was headache. No clinically relevant changes in laboratory or electrocardiogram (ECG) measurements were observed. Single oral doses of empagliflozin were rapidly absorbed, reaching peak levels after 1.0-2.1 hours. Increases in empagliflozin exposure were roughly dose-proportional and a dose-dependent increase in urinary glucose excretion was observed for empagliflozin doses up to 100 mg. After ingestion of 50 mg empagliflozin in conjunction with a high-fat, high-calorie meal, no clinically relevant changes in exposure were found, indicating that empagliflozin can be administered independent of food. Empagliflozin up to 800 mg did not generate clinically significant safety concerns in healthy male subjects. The pharmacokinetic properties of empagliflozin support once daily administration independent of food.

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

“…Increases in empagliflozin exposure were roughly dose-proportional and a dose-dependent increase in UGE was observed for empagliflozin doses up to 100 mg [26] .…”

“…In patients with T2DM and normal renal function, UGE increased according to the dose of SGLT2 given. However, for the doses used in clinical practice, no major changes in glucoselowering efficacy should be observed even if DDIs result in changing the plasma concentrations of dapagliflozin [20,21] , canagliflozin [22,23] or empagliflozin [24,26] by a factor two.…”

“…Dapagliflozin [19][20][21] Canagliflozin [19,22,23] Empagliflozin [19,24,26] [28] 0.86 (0.73-1.01) [32] 1.04 (0.97-1.11) [33] AUC [38] 1.09 (0.91-1.31) [31] 0.97 (0.76-1.24) [ [38] 1.03 (0.94-1.13) [39] 0.98 (0.91-1.05) [40] AUC 1.08 (1.03-1.12) 1.01 (0.96-1.06) [39] 0.99 (0.95-1.02) …”

Empagliflozin: the latest SGLT2 inhibitor on the block

“…After oral administration, time taken to achieve maximum concentration is 1.5 hours and the intake of food might decrease the absorption a bit, which is not relevant clinically. 11 The elimination half life is around 13 hours, with majority of drug being excreted in the urine itself, in 24 hours. Approximately 18% of the drug is excreted unchanged in the urine.…”

Empagliflozin and metformin combination therapy in Type 2 diabetes mellitus

“…15 Empaglifl ozin has a biphasic decline in plasma concentrations during the decay phase, with a terminal elimination half-life ranging from 8 to 13 hrs. 16 …”