Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus - PubMed (original) (raw)

Review

Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus

André J Scheen. Clin Pharmacokinet. 2014 Sep.

Free article

Erratum in

Abstract

Patients with type 2 diabetes mellitus 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, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients.

PubMed Disclaimer

Comment in

References

    1. Expert Opin Drug Metab Toxicol. 2013 May;9(5):529-50 - PubMed
    1. Acta Biomed. 2011 Aug;82(2):160-1 - PubMed
    1. Hepatogastroenterology. 2012 Jul-Aug;59(117):1522-5 - PubMed
    1. Eur J Clin Pharmacol. 2007 Jul;63(7):677-86 - PubMed
    1. Drug Metab Dispos. 2010 Nov;38(11):1944-53 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources