Renal impairment has no clinically relevant effect on the long-term exposure of linagliptin in patients with type 2 diabetes

Am J Ther. Nov-Dec 2013;20(6):618-21. doi: 10.1097/MJT.0b013e31826232dc.

Abstract

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor with a primarily nonrenal route of excretion. Consequently, renal impairment should not substantially affect drug exposure. This analysis was undertaken to compare steady-state trough concentrations of linagliptin among patients with type-2 diabetes receiving linagliptin 5 mg in phase 3 studies. Data were pooled from 3 randomized studies from the global phase 3 program of linagliptin (5 mg daily in each) in patients with type-2 diabetes. These studies were selected for their inclusion of pharmacokinetic data. Linagliptin plasma concentrations were available for 969 patients who were determined by estimated glomerular filtration rate to have normal renal function (n = 438), mild renal impairment (RI) (n = 429), moderate RI (n = 44), or severe RI (n = 58). In patients with normal renal function, the geometric mean linagliptin trough concentration (coefficient of variation) was 5.93 nmol/L (56.3%); in patients with mild, moderate, or severe RI, geometric mean concentrations were 6.07 nmol/L (62.9%), 7.34 nmol/L (58.6%), and 8.13 nmol/L (49.8%), respectively. In patients with type-2 diabetes, RI had a minor effect on linagliptin exposure. Therefore, neither dose-adjustment nor drug-related monitoring of estimated glomerular filtration rate is necessary for patients with RI.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Linagliptin
  • Male
  • Middle Aged
  • Purines / administration & dosage
  • Purines / pharmacokinetics*
  • Purines / therapeutic use
  • Quinazolines / administration & dosage
  • Quinazolines / pharmacokinetics*
  • Quinazolines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency / physiopathology*
  • Severity of Illness Index

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • Linagliptin