Comparative Clinical Study Between Empagliflozin Versus Pioglitazone in Non-diabetic Patients With Non-alcoholic Steatohepatitis

Summary

This study aims to evaluate the possible beneficial effect of empagliflozin versus pioglitazone on non-diabetic patients with non-alcoholic steatohepatitis (NASH). This study will be a randomized, comparative parallel study. The study will be conducted according to the ethical standards of Helsinki declaration in 1964 and its later amendments. The study duration will be 24 weeks. The patients will be randomized into two groups: Group 1: (Pioglitazone group; n=28) which will receive 30mg/day pioglitazone for 24 weeks. Group 2: (Empagliflozin group; n=28) which will receive 10mg/day empagliflozin for 24 weeks.

Timeline

Start

2022-11

Primary completion

2023-05

Completion

2024-11

Publications

• Background Abenavoli L, Greco M, Milic N, Accattato F, Foti D, Gulletta E, Luzza F. Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study. Nutrients. 2017 Aug 12;9(8):870. doi: 10.3390/nu9080870.
• Background Abenavoli L, Milic N, Di Renzo L, Preveden T, Medic-Stojanoska M, De Lorenzo A. Metabolic aspects of adult patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2016 Aug 21;22(31):7006-16. doi: 10.3748/wjg.v22.i31.7006.
• Background Androutsakos T, Nasiri-Ansari N, Bakasis AD, Kyrou I, Efstathopoulos E, Randeva HS, Kassi E. SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection. Int J Mol Sci. 2022 Mar 13;23(6):3107. doi: 10.3390/ijms23063107.
• Background Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006 Nov 30;355(22):2297-307. doi: 10.1056/NEJMoa060326.
• Background Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.
• Background Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.
• Background El-Haggar SM, Mostafa TM. Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. Hepatol Int. 2015 Jul;9(3):471-9. doi: 10.1007/s12072-015-9633-1. Epub 2015 May 9.
• Background Eriksson JW, Lundkvist P, Jansson PA, Johansson L, Kvarnstrom M, Moris L, Miliotis T, Forsberg GB, Riserus U, Lind L, Oscarsson J. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia. 2018 Sep;61(9):1923-1934. doi: 10.1007/s00125-018-4675-2. Epub 2018 Jul 3.
• Background Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001 Oct;15(10):1667-72. doi: 10.1046/j.1365-2036.2001.01083.x.
• Background Heo YJ, Lee N, Choi SE, Jeon JY, Han SJ, Kim DJ, Kang Y, Lee KW, Kim HJ. Empagliflozin Reduces the Progression of Hepatic Fibrosis in a Mouse Model and Inhibits the Activation of Hepatic Stellate Cells via the Hippo Signalling Pathway. Biomedicines. 2022 Apr 29;10(5):1032. doi: 10.3390/biomedicines10051032.
• Background Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, Bansal B, Kaur P, Jevalikar G, Gill HK, Choudhary NS, Mithal A. Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial). Diabetes Care. 2018 Aug;41(8):1801-1808. doi: 10.2337/dc18-0165. Epub 2018 Jun 12.
• Background Lee YH, Kim JH, Kim SR, Jin HY, Rhee EJ, Cho YM, Lee BW. Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness. J Korean Med Sci. 2017 Jan;32(1):60-69. doi: 10.3346/jkms.2017.32.1.60.
• Background Lian J, Fu J. Pioglitazone for NAFLD Patients With Prediabetes or Type 2 Diabetes Mellitus: A Meta-Analysis. Front Endocrinol (Lausanne). 2021 Apr 28;12:615409. doi: 10.3389/fendo.2021.615409. eCollection 2021.
• Background Lucero D, Zago V, Lopez GI, Graffigna M, Fainboim H, Miksztowicz V, Merono T, Belli S, Levalle O, Wikinski R, Brites F, Berg G, Schreier L. Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome. Clin Chim Acta. 2011 Jan 14;412(1-2):143-7. doi: 10.1016/j.cca.2010.09.025. Epub 2010 Sep 29.
• Background Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol. 2013 May;58(5):1007-19. doi: 10.1016/j.jhep.2012.11.021. Epub 2012 Nov 23.
• Background Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021 Jun 5;397(10290):2212-2224. doi: 10.1016/S0140-6736(20)32511-3. Epub 2021 Apr 21.
• Background Shimizu M, Suzuki K, Kato K, Jojima T, Iijima T, Murohisa T, Iijima M, Takekawa H, Usui I, Hiraishi H, Aso Y. Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019 Feb;21(2):285-292. doi: 10.1111/dom.13520. Epub 2018 Oct 2.
• Background Stefan N, Haring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 2019 Apr;7(4):313-324. doi: 10.1016/S2213-8587(18)30154-2. Epub 2018 Aug 30.
• Background Sviklane L, Olmane E, Dzerve Z, Kupcs K, Pirags V, Sokolovska J. Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes. J Gastroenterol Hepatol. 2018 Jan;33(1):270-276. doi: 10.1111/jgh.13814.
• Background Tomah S, Hamdy O, Abuelmagd MM, Hassan AH, Alkhouri N, Al-Badri MR, Gardner H, Eldib AH, Eid EA. Prevalence of and risk factors for non-alcoholic fatty liver disease (NAFLD) and fibrosis among young adults in Egypt. BMJ Open Gastroenterol. 2021 Oct;8(1):e000780. doi: 10.1136/bmjgast-2021-000780.
• Background Zhang Y, Liu X, Zhang H, Wang X. Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2022 Feb 24;13:836455. doi: 10.3389/fendo.2022.836455. eCollection 2022.

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