title: A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.
abstract: BACKGROUND
  DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise.
  
  
  METHODS
  We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229.
  
  
  RESULTS
  All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events.
  
  
  CONCLUSIONS
  DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
authors.forename: Kyu-Joeng
authors.initials: KJ
authors.lastname: Ahn
authors.forename: Nan-Hee
authors.initials: NH
authors.lastname: Kim
authors.forename: Hak-Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Choon-Hee
authors.initials: CH
authors.lastname: Chung
authors.forename: Kyung-Wan
authors.initials: KW
authors.lastname: Min
authors.forename: Yeon-Ah
authors.initials: YA
authors.lastname: Sung
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004032:Diet; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D038321:Glycemic Index; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D010879:Piperazines; C557982:4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
keywords: DPP-IV inhibitor; dose-finding study; monotherapy; type 2 diabetes mellitus