Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus.
BACKGROUND
To evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.


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).
Osaka Clinical Research Organization for Medicine-Clinic Osaka Japan.
Shigeto
S
Kanada
Nippon Boehringer Ingelheim Co., Ltd. Tokyo Japan.
Kazuki
K
Koiwai
Nippon Boehringer Ingelheim Co., Ltd. Tokyo Japan.
Atsushi
A
Taniguchi
Nippon Boehringer Ingelheim Co., Ltd. Hyogo Japan.
Akiko
A
Sarashina
Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield CT USA.
Leo
L
Seman
Boehringer Ingelheim Pharma GmbH & Co. KG Ingelheim Germany.
Hans J
HJ
Woerle
Diabetes; Empagliflozin; Sodium glucose cotransporter 2 inhibitor