Pharmacokinetic and pharmacodynamic study of ipragliflozin in Japanese patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled study

Aims: Ipragliflozin is a novel and highly selective sodium-glucose transporter 2 (SGLT2) inhibitor that reduces plasma glucose levels by enhancing urinary glucose excretion in patients with type 2 diabetes mellitus (T2DM). We examined the pharmacokinetic and pharmacodynamic characteristics of two oral doses of ipragliflozin in Japanese patients with T2DM. Methods: In this randomized, placebo-controlled, double-blind study, patients were treated with placebo, 50 mg or 100 mg ipragliflozin once daily for 14 days. Plasma and urine pharmacodynamic parameters were measured on Days -1 and 14, and pharmacokinetic parameters on Day 14. Pharmacodynamic characteristics included area under the curve (AUC) for plasma glucose and insulin for 0-3 h (AUC(0-3h)) and 0-24 h (AUC(0-24h)). Pharmacokinetic characteristics included AUC0-24h, maximum ipragliflozin concentration (C-max), and time to maximum plasma ipragliflozin concentration (t(max)). Results: Thirty patients were enrolled; 28 were included in pharmacokinetic/pharmacodynamic analyses and 30 in safety analyses. Administration of 50 and 100 mg ipragliflozin significantly reduced fasting plasma glucose, as well as the AUC0-3h and AUC0-24h for plasma glucose relative to placebo. Both doses of ipragliflozin also reduced AUC0-24h for insulin, body weight, and glycoalbumin, while urinary glucose excretion increased remarkably. Cmax and AUC0-24h were 1.7- and 1.9-fold higher, respectively, in the 100-mg group than in the 50-mg group. Conclusions: Ipragliflozin increased urinary glucose excretion and improved fasting and postprandial glucose, confirming its pharmacokinetic/pharmacodynamic properties in Japanese patients with T2DM. (C) 2014 Elsevier Ireland Ltd. All rights reserved.