Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes

Summary

The purpose of this study is to evaluate whether exenatide is superior to insulin glargine (after 24 weeks) in reducing liver fat content (by MRS) in patients with newly diagnosed type 2 diabetes mellitus and concomitant non-alcoholic fatty-liver disease(NAFLD).

Timeline

Start

2015-03

Primary completion

2017-11

Completion

2017-11

Publications

• Background Xu W, Bi Y, Sun Z, Li J, Guo L, Yang T, Wu G, Shi L, Feng Z, Qiu L, Li Q, Guo X, Luo Z, Lu J, Shan Z, Yang W, Ji Q, Yan L, Li H, Yu X, Li S, Zhou Z, Lv X, Liang Z, Lin S, Zeng L, Yan J, Ji L, Weng J. Comparison of the effects on glycaemic control and beta-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study). J Intern Med. 2015 Jan;277(1):137-50. doi: 10.1111/joim.12293. Epub 2014 Aug 5.
• Background Gupta NA, Mells J, Dunham RM, Grakoui A, Handy J, Saxena NK, Anania FA. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology. 2010 May;51(5):1584-92. doi: 10.1002/hep.23569.
• Background Sharma S, Mells JE, Fu PP, Saxena NK, Anania FA. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One. 2011;6(9):e25269. doi: 10.1371/journal.pone.0025269. Epub 2011 Sep 21.
• Background Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010 Mar;23(3):334-9. doi: 10.1038/ajh.2009.245. Epub 2009 Dec 17.
• Background Cuthbertson DJ, Irwin A, Gardner CJ, Daousi C, Purewal T, Furlong N, Goenka N, Thomas EL, Adams VL, Pushpakom SP, Pirmohamed M, Kemp GJ. 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. doi: 10.1371/journal.pone.0050117. Epub 2012 Dec 6.
• Background 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.
• Background Sathyanarayana P, Jogi M, Muthupillai R, Krishnamurthy R, Samson SL, Bajaj M. Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity (Silver Spring). 2011 Dec;19(12):2310-5. doi: 10.1038/oby.2011.152. Epub 2011 Jun 9.
• Background Shao N, Kuang HY, Hao M, Gao XY, Lin WJ, Zou W. Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes. Diabetes Metab Res Rev. 2014 Sep;30(6):521-9. doi: 10.1002/dmrr.2561.
• Background Juurinen L, Tiikkainen M, Hakkinen AM, Hakkarainen A, Yki-Jarvinen H. Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E829-35. doi: 10.1152/ajpendo.00133.2006. Epub 2006 Nov 7.
• Background ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
• Liu L, Wang R, Gao J, Yan J, Zhang J, Zhang Z, Liu J, Lin H, Rao S, Yao X, Wu W, Bian H, Wang X, Guo S, Gao X, Yan H. Insulin Glargine is More Suitable Than Exenatide in Preventing Muscle Loss in Non-Obese Type 2 Diabetic Patients with NAFLD. Exp Clin Endocrinol Diabetes. 2023 Nov;131(11):583-588. doi: 10.1055/a-2145-1004. Epub 2023 Jul 31.

Drugs

Indications