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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Bibliography

Picardi A, D’Avola D, Gentilucci UV, et al. Diabetes in chronic liver disease: from old concepts to new evidence. Diabetes Metab Res Rev. 2006;22(4):274–83.
Loria P, Lonardo A, Anania F. Liver and diabetes. A vicious circle. Hepatol Res. 2013;43(1):51–64.
Byrne CD. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. Diabet Med. 2012;29(9):1098–107.
Hsieh PS, Hsieh YJ. Impact of liver diseases on the development of type 2 diabetes mellitus. World J Gastroenterol. 2011;17(48):5240–5.
Garcia-Compean D, Jaquez-Quintana JO, Maldonado-Garza H. Hepatogenous diabetes. Current views of an ancient problem. Ann Hepatol. 2009;8(1):13–20.
Petrides AS, DeFronzo RA. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989;8(1):107–14.
Petrides AS, Vogt C, Schulze-Berge D, et al. Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis. Hepatology. 1994;19(3):616–27.
Mazza A, Fruci B, Garinis GA, et al. The role of metformin in the management of NAFLD. Exp Diabetes Res. 2012;2012:716404.
Fruci B, Giuliano S, Mazza A, et al. Nonalcoholic fatty liver: a possible new target for type 2 diabetes prevention and treatment. Int J Mol Sci. 2013;14(11):22933–66.
Scheen AJ. Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease. Expert Opin Drug Metab Toxicol. 2014;10(6):839–57.
Khan R, Foster GR, Chowdhury TA. Managing diabetes in patients with chronic liver disease. Postgrad Med. 2012;124(4):130–7.
Tolman KG, Fonseca V, Dalpiaz A, et al. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care. 2007;30(3):734–43.
Olaywi M, Bhatia T, Anand S, et al. Novel anti-diabetic agents in non-alcoholic fatty liver disease: a mini-review. Hepatobiliary Pancreat Dis Int. 2013;12(6):584–8.
Giorda CB, Nada E, Tartaglino B. Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine. Epub 2014 Feb 8.
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696–705.
Scheen AJ. A review of gliptins in 2011. Expert Opin Pharmacother. 2012;13(1):81–99.
Owens DR, Monnier L, Bolli GB. Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus. Diabetes Metab. 2013;39(6):485–96.
Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):728–42.
Blaslov K, Bulum T, Zibar K, et al. Incretin based therapies: a novel treatment approach for non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20(23):7356–65.
Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008;64(12):1147–61.
Srivastava B, Alexander GJ. Renal failure in chronic liver disease and the hepatorenal syndrome. Br J Hosp Med (Lond). 2011;72(9):497–503.
Scheen AJ. Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert Opin Drug Metab Toxicol. 2013;9(5):529–50.
Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010;12(8):648–58.
Golightly LK, Drayna CC, McDermott MT. Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012;51(8):501–14.
Vincent SH, Reed JR, Bergman AJ, et al. Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans. Drug Metab Dispos. 2007;35(4):533–8.
Migoya EM, Stevens CH, Bergman AJ, et al. Effect of moderate hepatic insufficiency on the pharmacokinetics of sitagliptin. Can J Clin Pharmacol 2009;16(1):e165–70.
Arase Y, Kawamura Y, Seko Y, et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by non-alcoholic fatty liver disease. Hepatol Res. 2013;43(11):1163–8.
Iwasaki T, Yoneda M, Inamori M, et al. Sitagliptin as a novel treatment agent for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology 2011;58 (112):2103–5.
Itou M, Kawaguchi T, Taniguchi E, et al. Dipeptidyl Peptidase IV inhibitor improves insulin resistance and steatosis in a refractory nonalcoholic fatty liver disease patient: a case report. Case Rep Gastroenterol. 2012;6(2):538–44.
Fukuhara T, Hyogo H, Ochi H, et al. Efficacy and safety of sitagliptin for the treatment of nonalcoholic fatty liver disease with type 2 diabetes mellitus. Hepatogastroenterology. 2014;61(130):323–8.
Yilmaz Y, Yonal O, Deyneli O, et al. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg. 2012;75(2):240–4.
Arase Y, Suzuki F, Kobayashi M, et al. Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus. Hepatol Res. 2011;41(6):524–9.
Iwasaki T, Tomeno W, Yoneda M, et al. Non-alcoholic fatty liver disease adversely affects the glycemic control afforded by sitagliptin. Hepatogastroenterology. 2012;59(117):1522–5.
Gooßen K, Gräber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab. 2012;14(12):1061–72.
Toyoda-Akui M, Yokomori H, Kaneko F, et al. A case of drug-induced hepatic injury associated with sitagliptin. Intern Med. 2011;50(9):1015–20.
Gross BN, Cross LB, Foard J, et al. Elevated hepatic enzymes potentially associated with sitagliptin. Ann Pharmacother. 2010;44(2):394–5.
Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354(7):731–9.
He YL. Clinical pharmacokinetics and pharmacodynamics of vildagliptin. Clin Pharmacokinet. 2012;51(3):147–62.
He YL, Sabo R, Campestrini J, et al. The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin. Eur J Clin Pharmacol. 2007;63(7):677–86.
Ligueros-Saylan M, Foley JE, Schweizer A, et al. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of phase II and III clinical trials. Diabetes Obes Metab. 2010;12(6):495–509.
Schweizer A, Dejager S, Foley JE, et al. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies. Vasc Health Risk Manag. 2011;7:49–57.
Patel C, Castaneda L, Frevert U, et al. Single-dose pharmacokinetics and safety of saxagliptin in subjects with hepatic impairment compared with healthy subjects [abstract no. 537-P]. Diabetes 2008 57 Suppl 1:A160.
Boulton DW, Li L, Frevert EU, et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin Pharmacokinet. 2011;50(4):253–65.
Ali S, Fonseca V. Saxagliptin overview: special focus on safety and adverse effects. Expert Opin Drug Saf. 2013;12(1):103–9.
Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317–26.
Scheen AJ. Linagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation). Expert Opin Drug Metab Toxicol. 2011;7(12):1561–76.
Graefe-Mody U, Rose P, Retlich S, et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br J Clin Pharmacol. 2012;74(1):75–85.
Schernthaner G, Barnett AH, Emser A, et al. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2012;14(5):470–8.
Kutoh E. Probable linagliptin-induced liver toxicity: a case report. Diabetes Metab. 2014;40(1):82–4.
Karim A, Fleck P, Dorsey D, et al. Single dose pharmacokinetics of alogliptin benzoate(SYR-322) in subjects with moderate hepatic impairment [abstract no. 107]. J Clin Pharmacol. 2007;47(9):1207.
Food and Drug Administration, Center for Drug Evaluation and Research. Clinical Pharmacology and Biopharmaceutics Reviews: Application number: 022271Orig1s000 (Nesina, alogliptin). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf. Accessed 10 Apr 2014.
Scott LJ. Alogliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70(15):2051–72.
White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327–35.
Kajiwara A, Saruwatari J, Sakata M, et al. Risk factors for adverse symptoms during dipeptidyl peptidase-IV inhibitor therapy: a questionnaire-based study carried out by the Japan Pharmaceutical Association Drug Event Monitoring project in Kumamoto Prefecture. Drug Saf. 2013;36(10):981–7.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55(6):1577–96.
Jespersen MJ, Knop FK, Christensen M. GLP-1 agonists for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol. 2013;9(1):17–29.
Flint A, Nazzal K, Jagielski P, et al. Influence of hepatic impairment on pharmacokinetics of the human GLP-1 analogue, liraglutide. Br J Clin Pharmacol. 2010;70(6):807–14.
Copley K, McCowen K, Hiles R, et al. Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab. 2006;7(4):367–74.
Fan H, Pan Q, Xu Y, et al. Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. Arq Bras Endocrinol Metabol. 2013;57(9):702–8.
Cuthbertson DJ, Irwin A, Gardner CJ, et al. Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One. 2012;7(12):e50117.
Shao N, Kuang HY, Hao M, et al. Effects of exenatide on obesity and NAFLD with elevated liver enzymes in patients with type 2 diabetes. Diabetes Metab Res Rev. Epub 2014 May 13. doi:10.1002/dmrr.2561.
Kenny PR, Brady DE, Torres DM, et al. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010;105(12):2707–9.
Xu F, Li Z, Zheng X, et al. SIRT1 mediates the effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis. Diabetes. Epub 2014 Jun 19. pii: DB_140263.
Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007;29(1):139–53.
Malm-Erjefalt M, Bjornsdottir I, Vanggaard J, et al. Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010;38(11):1944–53.
Armstrong MJ, Houlihan DD, Rowe IA, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther. 2013;37(2):234–42.
Ohki T, Isogawa A, Iwamoto M, et al. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone. ScientificWorldJournal. 2012;2012:496453.
Kahal H, Abouda G, Rigby AS, et al. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). Epub 2013 Nov 21. doi:10.1111/cen.12369.
D’Amico E. Efficacy of liraglutide in a patient with type 2 diabetes and cryptogenic cirrhosis. Acta Biomed. 2011;82(2):160–1.
Eguchi Y, Kitajima Y, Hyogo H, et al. Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J). Hepatol Res. Epub 2014 May 4. doi:10.1111/hepr.12351.
Kern E, VanWagner LB, Yang GY, et al. Liraglutide-induced autoimmune hepatitis. JAMA Intern Med. 2014;174(6):984–7.
Forst T, Pfutzner A. Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes mellitus. Expert Opin Pharmacother. 2013;14(16):2281–96.
European Medicines Agency. Assessment report: Lyxumia (lixisenatide). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Public_assessment_report/human/002445/WC500140449.pdf?. Accessed 10 Apr 2014.
Balaban YH, Korkusuz P, Simsek H, et al. Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol. 2007;6(4):242–50.
Itou M, Kawaguchi T, Taniguchi E, et al. Dipeptidyl peptidase-4: a key player in chronic liver disease. World J Gastroenterol. 2013;19(15):2298–306.
Armstrong MJ, Barton D, Gaunt P, et al. Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial. BMJ Open. 2013;3(11):e003995.
Bernsmeier C, Meyer-Gerspach AC, Blaser LS, et al. Glucose-induced glucagon-like peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease. PLoS One. 2014;9(1):e87488.
Muscelli E, Mari A, Casolaro A, et al. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes. 2008;57(5):1340–8.