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

Scheen, André

doi:10.1007/s40262-014-0157-y

Article (Scientific journals)

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

Scheen, André

2014 • In Clinical Pharmacokinetics, 53 (9), p. 773-85

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https://hdl.handle.net/2268/172391

DOI
10.1007/s40262-014-0157-y

PubMed
25091053

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Abstract :

[en] 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.

Disciplines :

Endocrinology, metabolism & nutrition
Gastroenterology & hepatology

Author, co-author :

Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques

Language :

English

Title :

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

Publication date :

2014

Journal title :

Clinical Pharmacokinetics

ISSN :

0312-5963

eISSN :

1179-1926

Publisher :

Adis International, United Kingdom

Volume :

Issue :

Pages :

773-85

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 29 September 2014

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