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Expert Opin Drug Metab Toxicol. 2014 Jun;10(6):839-57. doi: 10.1517/17425255.2014.902444. Epub 2014 Mar 26.

Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.

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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 ;



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).


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.


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.


chronic liver disease; cirrhosis; glucose-lowering therapy; hepatic impairment; hepatotoxicity; oral antidiabetic agent; pharmacokinetics; type 2 diabetes mellitus

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