title: Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the long-term safety and efficacy of linagliptin as add-on therapy to one approved oral antidiabetic drug (OAD) in Japanese patients with type 2 diabetes mellitus and insufficient glycaemic control.
  
  
  METHODS
  This 52-week, multicentre, open-label, parallel-group study evaluated once-daily linagliptin 5 mg as add-on therapy to one OAD [biguanide, glinide, glitazone, sulphonylurea (SU) or α-glucosidase inhibitors (A-GI)] in 618 patients. After a 2-week run-in, patients on SU or A-GI were randomized to either linagliptin (once daily, 5 mg) or metformin (twice or thrice daily, up to 2250 mg/day) as add-on therapy. Patients receiving the other OADs received linagliptin add-on therapy (non-randomized).
  
  
  RESULTS
  Adverse events were mostly mild or moderate, and rates were similar across all groups. Hypoglycaemic events were rare, except in the SU group. Overall, 26 (5.8%) hypoglycaemic events were reported in patients receiving linagliptin (non-randomized). Hypoglycaemic events were similar for linagliptin and metformin added to A-GI (1/61 vs. 2/61, respectively) or SU (17/124 vs. 10/63, respectively). Significant reductions in glycated haemoglobin (HbA1c) levels (between -0.7 and -0.9%) occurred throughout the study period for the background therapy groups that received linagliptin (baseline HbA1c 7.9-8.1%). The decline in HbA1c levels was indistinguishable between linagliptin and metformin groups when administered as add-on therapy to A-GI or SU.
  
  
  CONCLUSIONS
  Once-daily linagliptin showed safety and tolerability over 1 year and provided effective add-on therapy leading to significant HbA1c reductions, similar to metformin, over 52 weeks in Japanese patients.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. inagaki@metab.kuhp.kyoto-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: H
authors.initials: H
authors.lastname: Watada
authors.forename: M
authors.initials: M
authors.lastname: Murai
authors.forename: T
authors.initials: T
authors.lastname: Kagimura
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D044466:Asian People / Q000706:statistics & numerical data; D001645:Biguanides / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007564:Japan / Q000453:epidemiology; D000069476:Linagliptin; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001645:Biguanides; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; D011687:Purines; D011799:Quinazolines; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; clinical trial; diabetes mellitus; glycaemic control; phase III study; type 2 diabetes