title: Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, double-blind, placebo-controlled, phase II study.
abstract: OBJECTIVE
  Luseogliflozin is a selective sodium glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). This phase II study was conducted to confirm the efficacy and safety of luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with T2DM.
  
  
  METHODS
  Patients with hemoglobin A1c (HbA1c) of 6.9-10.5% on diet therapy were randomized in a double-blind manner to treatment with 1, 2.5, 5, or 10 mg luseogliflozin or placebo for 12 weeks (n = 56, 56, 54, 58, and 58, respectively).
  
  
  BACKGROUND
  Japan Pharmaceutical Information Center (identifier: Japic CTI-101191).
  
  
  METHODS
  The primary endpoint was the change in HbA1c from baseline to the end of treatment. Other endpoints included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight. Adverse events were recorded throughout the study.
  
  
  RESULTS
  HbA1c decreased significantly at the end of treatment in the 1, 2.5, 5, and 10 mg luseogliflozin groups compared with placebo (-0.29, -0.39, -0.46, and -0.43%, respectively, versus +0.22%; all P < 0.001), as did FPG and PPG (all P < 0.001). Body weight also decreased significantly in all luseogliflozin groups compared with placebo (all P < 0.001). The incidence rates of adverse events (40.0-50.0%) were not significantly different among the five groups. The overall incidence of hypoglycemia was low. Limitations of this study include the short study duration and the relatively small sample size.
  
  
  CONCLUSIONS
  In Japanese patients with T2DM, luseogliflozin was well tolerated, improved glycemic control, and reduced body weight over 12 weeks of treatment at all tested doses. Doses of ≥2.5 mg achieved similar improvements in glycemic control.
authors.affiliation: Kansai Electric Power Hospital , Osaka , Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
authors.forename: Michito
authors.initials: M
authors.lastname: Ubukata
authors.forename: Soichi
authors.initials: S
authors.lastname: Sakai
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Samukawa
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D013012:Sorbitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013012:Sorbitol; C517652:hemoglobin A1c protein, human; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol
keywords: Japanese; Luseogliflozin; Monotherapy; Randomized phase II study; SGLT2 inhibitor; type 2 diabetes mellitus