Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes

Diabetes Obes Metab. 2013 Sep;15(9):833-43. doi: 10.1111/dom.12110. Epub 2013 May 3.

Abstract

Aims: 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.

Keywords: DPP-4 inhibitor; clinical trial; diabetes mellitus; glycaemic control; phase III study; type 2 diabetes.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Asian People / statistics & numerical data
  • Biguanides / administration & dosage
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Japan / epidemiology
  • Linagliptin
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Purines / administration & dosage*
  • Quinazolines / administration & dosage*
  • Sulfonylurea Compounds / administration & dosage
  • Thiazolidinediones / administration & dosage
  • Time Factors
  • Treatment Outcome

Substances

  • Biguanides
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Linagliptin
  • Metformin