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

Abstract

AimsIpragliflozin 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. MethodsIn this randomized, placebo-controlled, double-blind study, patients were treated with placebo, 50mg or 100mg 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 0–3h (AUC0–3h) and 0–24h (AUC0–24h). Pharmacokinetic characteristics included AUC0–24h, maximum ipragliflozin concentration (Cmax), and time to maximum plasma ipragliflozin concentration (tmax). ResultsThirty patients were enrolled; 28 were included in pharmacokinetic/pharmacodynamic analyses and 30 in safety analyses. Administration of 50 and 100mg 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. ConclusionsIpragliflozin increased urinary glucose excretion and improved fasting and postprandial glucose, confirming its pharmacokinetic/pharmacodynamic properties in Japanese patients with T2DM.