title: Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.
abstract: BACKGROUND
  Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI).
  
  
  METHODS
  An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned.
  
  
  CONCLUSIONS
  Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and α-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin.
authors.affiliation: University of Liège, CHU Sart Tilman (B35), Center for Interdisciplinary Research on Medicines (CIRM), Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine , B-4000 Liege 1 , Belgium +32 4 3667238 ; +32 4 3667068 ; andre.scheen@chu.ulg.ac.be.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D048550:Hepatic Insufficiency / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism; D008687:Metformin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin
keywords: chronic liver disease; cirrhosis; glucose-lowering therapy; hepatic impairment; hepatotoxicity; oral antidiabetic agent; pharmacokinetics; type 2 diabetes mellitus