Probable linagliptin-induced liver toxicity: a case report

Diabetes Metab. 2014 Feb;40(1):82-84. doi: 10.1016/j.diabet.2013.09.009. Epub 2013 Oct 25.

Abstract

Aim: Unlike other dipeptidyl peptidase 4 (DPP-4) inhibitors, the excretion of linagliptin is mainly through a biliary route. Despite this fact, liver injury with linagliptin has thus far not been reported in the literature. However, this report describes the first case of probable linagliptin-induced liver toxicity.

Methods: The clinical history, diagnosis, investigations and drug treatment of the patient are reviewed here.

Results: A 58-year-old Japanese woman presented with fatigue, nausea, jaundice and marked elevations of hepatic enzymes 4weeks after starting linagliptin 5mg/day as monotherapy. No other medications were taken, and imaging studies revealed no other obvious causes of hepatic injury. Tests for viral serology and antinuclear antigen were negative. Symptoms disappeared and the levels of hepatic parameters (serum aminotransferases and biliary enzymes) slowly recovered after discontinuation of linagliptin. The slow recovery process may have been due to the very long half-life of the drug. The patient's Naranjo scale score was 6 and RUCAM score was 7.

Conclusion: Although linagliptin currently carries no liver warnings, it may be necessary to monitor hepatic function in some patients upon administration of this drug until further evidence is obtained.

Keywords: DPP-4 inhibitors; Drug-induced liver toxicity; Linagliptin.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Chemical and Drug Induced Liver Injury / complications
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Dose-Response Relationship, Drug
  • Fatigue / etiology
  • Female
  • Half-Life
  • Humans
  • Jaundice / etiology
  • Linagliptin
  • Metabolic Clearance Rate
  • Middle Aged
  • Nausea / etiology
  • Purines / administration & dosage
  • Purines / adverse effects*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects*

Substances

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