Role of Exenatide in NASH-a Pilot Study

Summary

We hypothesize that exenatide (Byetta), a GLP-1 agonist administered subcutaneously for 24-28 weeks improves liver histology in diabetic patients with biopsy-proven NASH.

Timeline

Start

2006-08

Primary completion

2010-08

Completion

2010-08

Publications

• Background Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014.
• Background Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004 Mar;2(3):262-5. doi: 10.1016/s1542-3565(04)00014-x.
• Background Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, Taylor K, Kim D, Aisporna M, Wang Y, Baron AD. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003 Jul;88(7):3082-9. doi: 10.1210/jc.2002-021545.
• Background Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004 Jan;39(1):188-96. doi: 10.1002/hep.20012.
• Background Shadid S, Jensen MD. Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity. Clin Gastroenterol Hepatol. 2003 Sep;1(5):384-7. doi: 10.1053/s1542-3565(03)00198-8.
• Background Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003 Oct;38(4):1008-17. doi: 10.1053/jhep.2003.50420.
• Background Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP. Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem. 1990 Nov 25;265(33):20259-62.
• Background Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992 Apr 15;267(11):7402-5.
• Background Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem. 1997 Feb 14;272(7):4108-15. doi: 10.1074/jbc.272.7.4108.
• Background Greig NH, Holloway HW, De Ore KA, Jani D, Wang Y, Zhou J, Garant MJ, Egan JM. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia. 1999 Jan;42(1):45-50. doi: 10.1007/s001250051111.
• Results Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available.

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Indications