title: Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo and voglibose in Japanese patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This study enrolled patients with inadequately controlled T2DM who were previously treated with one or two oral antidiabetics or were drug naÏve. After a 2 to 4-week washout and placebo run-in, 561 patients were randomized (2 : 2 : 2 : 1) to double-blind treatment with linagliptin 5 or 10 mg qd, voglibose 0.2 mg tid or placebo. The primary endpoint was the change from baseline in haemoglobin A1c (HbA1c) with linagliptin vs. placebo after 12 weeks and vs. voglibose after 26 weeks.
  
  
  RESULTS
  Baseline characteristics were well balanced across treatment groups (overall mean HbA1c was 8.01%). The adjusted mean (95% confidence interval) treatment differences at week 12 were -0.87% (-1.04, -0.70; p < 0.0001) and -0.88% (-1.05, -0.71; p < 0.0001) for linagliptin 5 and 10 mg vs. placebo and at week 26 were -0.32% (-0.49, -0.15; p = 0.0003) and -0.39% (-0.56, -0.21; p < 0.0001) for linagliptin 5 and 10 mg vs. voglibose. At week 12, mean HbA1c was 7.58, 7.48 and 8.34% in patients receiving linagliptin 5 mg, linagliptin 10 mg and placebo, respectively. At week 26, mean HbA1c was 7.63% with linagliptin 5 mg, 7.50% with linagliptin 10 mg and 7.91% with voglibose. Drug-related adverse event rates were comparable across treatment groups over 12 weeks (9.4% linagliptin 5 mg, 8.8% linagliptin 10 mg and 10.0% placebo) and 26 weeks (11.3% linagliptin 5 mg, 10.6% linagliptin 10 mg and 18.5% voglibose). There were no documented cases of hypoglycaemia.
  
  
  CONCLUSIONS
  Linagliptin showed superior glucose-lowering efficacy and comparable safety and tolerability to both placebo and voglibose in Japanese patients with T2DM.
authors.affiliation: Sportology Centre, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kawamori
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: E
authors.initials: E
authors.lastname: Araki
authors.forename: H
authors.initials: H
authors.lastname: Watada
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Horie
authors.forename: A
authors.initials: A
authors.lastname: Sarashina
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: K A
authors.initials: KA
authors.lastname: Dugi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007294:Inositol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007564:Japan; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; D007294:Inositol; C102817:voglibose