Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus

Abstract

Introduction: To evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.

Materials and methods: In this 4-week, multiple dose, randomized, parallel-group, double-blind, placebo-controlled trial, patients (n = 100) were randomized to receive 1, 5, 10 or 25 mg of empagliflozin, or placebo once daily. Key end-points were urinary glucose excretion (UGE), fasting plasma glucose (FPG) and eight-point glucose profile.

Results: Data are presented for 1, 5, 10, 25 mg of empagliflozin and placebo groups, respectively. Adjusted mean changes from baseline to day 27 in UGE were 40.8, 77.1, 80.9, 93.0 and -2.1 g (P < 0.0001 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 28 in FPG were -1.56, -1.96, -2.31, -2.37 and -0.86 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 27 in eight-point glucose profile were -1.96, -2.21, -2.42, -2.54 and -0.97 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Empagliflozin reached peak plasma concentration 1.5-2 h after dosing. Mean steady state terminal elimination half-lives ranged from 13.2 to 18.0 h. Of 100 patients, 25 experienced an adverse event, occurring more frequently for empagliflozin (29.1%) than placebo (9.5%); frequency was not dose related.

Conclusions: In Japanese patients with type 2 diabetes mellitus, empagliflozin at doses up to 25 mg once daily for 4 weeks was well tolerated and resulted in significant improvements in glycemic control compared with placebo. This trial was registered with ClinicalTrials.gov (no. NCT00885118).

Keywords: Diabetes; Empagliflozin; Sodium glucose cotransporter 2 inhibitor.

Figures

Figure 1

Disposition of patients. qd, Once daily.

Figure 2

Adjusted mean (standard error [SE]) changes from baseline in (a) cumulative urinary glucose excretion (UGE) after first (day 1) and multiple (days 27 and 28†) drug administration, (b) fasting plasma glucose (FPG) after multiple drug administration (day 28), (c) eight‐point glucose profile after first (day 1) and multiple drug administration (day 27) and (d) glycated hemoglobin (HbA1c) after multiple drug administration (day 28). †A meal tolerance test was carried out on day 28. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs placebo.