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Diabetes Metab Syndr Obes. 2019 Jul 03;12:1001-1012. doi: 10.2147/DMSO.S212715. eCollection 2019.

SGLT-2 inhibitors as promising therapeutics for non-alcoholic fatty liver disease: pathophysiology, clinical outcomes, and future directions.

Diabetes, metabolic syndrome and obesity : targets and therapy

Naser Eddin Gharaibeh, Marie-Noel Rahhal, Leili Rahimi, Faramarz Ismail-Beigi

Affiliations

  1. Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA.

PMID: 31308716 PMCID: PMC6613609 DOI: 10.2147/DMSO.S212715

Abstract

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a major expanding national and international health problem. Despite numerous investigations using a variety of therapeutic agents, the positive result on any single medication has not been established enough to gain widespread approval. This is in part related to concerns regarding side effects of agents, but is also related to the complex etiology of NAFLD. An often discussed question has been whether insulin resistance that is frequently present in those with NAFLD is a cause of NAFLD or is merely associated with the condition. Nevertheless, it is clear that a very high proportion of patients with NAFLD are obese, have elements of metabolic syndrome, or have type 2 diabetes (T2DM). Also, much progress has been made toward a better understanding of the pathophysiology of NAFLD. Life-style interventions resulting in weight loss remain the foundation for the prevention and treatment of NAFLD. In addition, agents such as Vitamin E and pioglitazone as well as other glycemia-lowering agents including Glucagon Like Peptide-1 (GLP-1) receptor agonists and Sodium Glucose Contransporter-2 inhibitors (SGLT-2i(s)) exhibit positive effects on the clinical course of NAFLD. This narrative review summarizes the current understanding of the diagnosis, epidemiology, and pathophysiology of NAFLD and specifically focuses on the efficacy of SGLT2i(s) as a potentially promising group of agents for the management of patients with NAFLD.

Keywords: beta-oxidation; de novo lipid synthesis; fatty liver; insulin resistance; liver biopsy

Conflict of interest statement

The authors report no conflicts of interest in this work.

References

  1. N Engl J Med. 2002 Apr 18;346(16):1221-31 - PubMed
  2. Obes Surg. 2004 May;14(5):635-7 - PubMed
  3. J Pharmacol Exp Ther. 2007 Jan;320(1):323-30 - PubMed
  4. N Engl J Med. 2006 Nov 30;355(22):2297-307 - PubMed
  5. Br J Cancer. 2007 Oct 8;97(7):1005-8 - PubMed
  6. J Clin Invest. 2008 Mar;118(3):829-38 - PubMed
  7. Am J Clin Nutr. 1991 Oct;54(4):684-8 - PubMed
  8. Gastroenterology. 2008 Oct;135(4):1176-84 - PubMed
  9. N Engl J Med. 2010 May 6;362(18):1675-85 - PubMed
  10. Lancet. 2010 Jun 26;375(9733):2223-33 - PubMed
  11. BMJ. 2010 Nov 04;341:c5702 - PubMed
  12. World J Gastroenterol. 2010 Nov 14;16(42):5286-96 - PubMed
  13. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16381-5 - PubMed
  14. JAMA. 2011 Oct 12;306(14):1549-56 - PubMed
  15. Diabetes Ther. 2010 Dec;1(2):57-92 - PubMed
  16. Am J Gastroenterol. 1990 Oct;85(10):1349-55 - PubMed
  17. J Hepatol. 2012 Jun;56(6):1384-91 - PubMed
  18. Trends Endocrinol Metab. 2013 May;24(5):257-68 - PubMed
  19. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55 - PubMed
  20. Diabetologia. 2013 Dec;56(12):2582-92 - PubMed
  21. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):656-65 - PubMed
  22. Eur J Pharmacol. 2014 Mar 15;727:66-74 - PubMed
  23. Nature. 2014 Jun 5;510(7503):84-91 - PubMed
  24. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62 - PubMed
  25. Gastroenterology. 2015 Aug;149(2):367-78.e5; quiz e14-5 - PubMed
  26. Nat Med. 2015 May;21(5):512-7 - PubMed
  27. JAMA. 2015 Jun 9;313(22):2263-73 - PubMed
  28. Nutrition. 2015 Jul-Aug;31(7-8):923-30 - PubMed
  29. World J Hepatol. 2015 Jun 28;7(12):1679-84 - PubMed
  30. J Diabetes Complications. 2015 Nov-Dec;29(8):1295-303 - PubMed
  31. Diabetes Metab. 2016 Feb;42(1):25-32 - PubMed
  32. Lancet. 2016 Feb 13;387(10019):679-90 - PubMed
  33. J Intern Med. 2016 May;279(5):485-93 - PubMed
  34. Diabetes. 2016 May;65(5):1190-5 - PubMed
  35. Clin Drug Investig. 2016 Apr;36(4):313-9 - PubMed
  36. PLoS One. 2016 Mar 15;11(3):e0151511 - PubMed
  37. J Physiol. 2016 Aug 1;594(15):4425-38 - PubMed
  38. Diabetologia. 2016 Jun;59(6):1112-20 - PubMed
  39. N Engl J Med. 2016 Jul 28;375(4):311-22 - PubMed
  40. Metabolism. 2016 Aug;65(8):1183-95 - PubMed
  41. Hepatology. 2016 Nov;64(5):1577-1586 - PubMed
  42. Diabetes Care. 2016 Nov;39(11):2036-2041 - PubMed
  43. Gut. 2017 Jan;66(1):180-190 - PubMed
  44. Hepatol Res. 2017 Sep;47(10):1072-1078 - PubMed
  45. Int J Mol Sci. 2016 Dec 11;17(12): - PubMed
  46. Gastroenterology. 2017 Apr;152(5):1090-1099.e1 - PubMed
  47. Stroke. 2017 May;48(5):1218-1225 - PubMed
  48. J Gen Intern Med. 2017 Sep;32(9):1044-1051 - PubMed
  49. N Engl J Med. 2017 Aug 17;377(7):644-657 - PubMed
  50. Diabetes Care. 2017 Oct;40(10):1364-1372 - PubMed
  51. Am J Physiol Endocrinol Metab. 2017 Nov 1;313(5):E563-E576 - PubMed
  52. Nutrients. 2017 Sep 06;9(9):null - PubMed
  53. Curr Ther Res Clin Exp. 2017 Jul 08;87:13-19 - PubMed
  54. Gene Expr. 2018 May 18;18(2):89-101 - PubMed
  55. J Intern Med. 2018 Apr;283(4):356-370 - PubMed
  56. Int J Mol Sci. 2018 Jan 03;19(1):null - PubMed
  57. World J Gastroenterol. 2017 Dec 21;23(47):8263-8276 - PubMed
  58. Diabetes Ther. 2018 Feb;9(1):285-295 - PubMed
  59. Sci Rep. 2018 Feb 5;8(1):2362 - PubMed
  60. Hepatol Commun. 2017 Feb 27;1(1):46-52 - PubMed
  61. J Diabetes Res. 2018 Jan 8;2018:6470137 - PubMed
  62. Cardiovasc Diabetol. 2018 Apr 27;17(1):62 - PubMed
  63. Diabetes Care. 2018 Aug;41(8):1801-1808 - PubMed
  64. Diabetologia. 2018 Sep;61(9):1923-1934 - PubMed
  65. Diabetologia. 2018 Oct;61(10):2155-2163 - PubMed
  66. Eur J Gastroenterol Hepatol. 2018 Oct;30(10):1103-1115 - PubMed
  67. Obes Sci Pract. 2018 Aug 22;4(5):477-482 - PubMed
  68. Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2207-2216 - PubMed
  69. N Engl J Med. 2019 Jan 24;380(4):347-357 - PubMed
  70. J Diabetes Investig. 2019 Jul;10(4):1004-1011 - PubMed
  71. Sci Transl Med. 2018 Nov 21;10(468):null - PubMed
  72. Curr Pharm Des. 2018;24(38):4574-4586 - PubMed
  73. Diabetes Care. 2019 Apr;42(4):585-593 - PubMed
  74. Gastroenterology. 1998 Apr;114(4):842-5 - PubMed

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