Skip to main content

Advertisement

SpringerLink
Log in

Anti-obesity Medications for the Management of Nonalcoholic Fatty Liver Disease

  • Metabolism (M Dalamaga, Section Editor)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Obesity is closely associated with nonalcoholic fatty liver disease (NAFLD), a highly prevalent disease without any approved medication. The aim of this review was to summarize the evidence on the effect of anti-obesity medications on NAFLD, especially focusing on hepatic histology.

Recent Findings

Orlistat and some glucagon-like peptide-1 receptor analogs, including liraglutide and semaglutide, have beneficial effects on hepatic steatosis and inflammation, but not fibrosis. Other anti-obesity medications, including lorcaserin, setmelanotide, phentermine hydrochloric, phentermine/topiramate, and naltrexone/bupropion, have been minimally investigated in NAFLD. Furthermore, medications like sodium-glucose cotransporter-2 inhibitors and farnesoid X receptor have shown beneficial effects in both NAFLD and obesity, but they have not been licensed for either disease.

Summary

Liraglutide, semaglutide, and orlistat may be currently used in selected patients with obesity and NAFLD. Further research is warranted, since targeting obesity may provide additional benefits on its comorbidities, including NAFLD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Younossi ZM, Stepanova M, Younossi Y, Golabi P, Mishra A, Rafiq N, et al. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut. 2020;69:564–8. https://doi.org/10.1136/gutjnl-2019-318813.

    Article  PubMed  Google Scholar 

  2. Polyzos SA, Mantzoros CS. Nonalcoholic fatty future disease. Metabolism. 2016;65:1007–16. https://doi.org/10.1016/j.metabol.2015.12.009.

    Article  CAS  PubMed  Google Scholar 

  3. Makri E, Goulas A, Polyzos SA. Epidemiology, pathogenesis, diagnosis and emerging treatment of nonalcoholic fatty liver disease. Arch Med Res. 2021;52:25–37. https://doi.org/10.1016/j.arcmed.2020.11.010.

    Article  CAS  PubMed  Google Scholar 

  4. Polyzos SA, Kechagias S, Tsochatzis E. Review article: non-alcoholic fatty liver disease and cardiovascular diseases—associations and treatment considerations. Aliment Pharmacol Ther. 2021;54:1013–55. https://doi.org/10.1111/apt.16575.

    Article  PubMed  Google Scholar 

  5. Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083–96. https://doi.org/10.1016/S0140-6736(09)60318-4.

    Article  PubMed  Google Scholar 

  6. Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17:510–9. https://doi.org/10.1111/obr.12407.

    Article  CAS  PubMed  Google Scholar 

  7. Polyzos SA, Kountouras J, Mantzoros CS. Adipose tissue, obesity and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017;42:92–108. https://doi.org/10.23736/S0391-1977.16.02563-3.

  8. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73:202–9. https://doi.org/10.1016/j.jhep.2020.03.039.

    Article  PubMed  Google Scholar 

  9. Eslam M, Sanyal AJ, George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158:1999–2014. https://doi.org/10.1053/j.gastro.2019.11.312.

    Article  CAS  PubMed  Google Scholar 

  10. Polyzos SA, Kang ES, Tsochatzis EA, Kechagias S, Ekstedt M, Xanthakos S, et al. Commentary: Nonalcoholic or metabolic dysfunction-associated fatty liver disease? The epidemic of the 21st century in search of the most appropriate name. Metabolism. 2020;113: 154413. https://doi.org/10.1016/j.metabol.2020.154413.

    Article  CAS  PubMed  Google Scholar 

  11. Mintziori G, Polyzos SA. Emerging and future therapies for nonalcoholic steatohepatitis in adults. Expert Opin Pharmacother. 2016;17:1937–46. https://doi.org/10.1080/14656566.2016.1225727.

    Article  CAS  PubMed  Google Scholar 

  12. Polyzos SA, Kang ES, Boutari C, Rhee EJ, Mantzoros CS. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020;111S: 154203. https://doi.org/10.1016/j.metabol.2020.154203.

    Article  CAS  PubMed  Google Scholar 

  13. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol. 2018;24:3361–73. https://doi.org/10.3748/wjg.v24.i30.3361.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019;92:82–97. https://doi.org/10.1016/j.metabol.2018.11.014.

    Article  CAS  PubMed  Google Scholar 

  15. Hannah WN Jr, Harrison SA. Effect of weight loss, diet, exercise, and bariatric surgery on nonalcoholic fatty liver disease. Clin Liver Dis. 2016;20:339–50. https://doi.org/10.1016/j.cld.2015.10.008.

    Article  PubMed  Google Scholar 

  16. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–78. https://doi.org/10.1053/j.gastro.2015.04.005.

    Article  PubMed  Google Scholar 

  17. Upadhyay J, Polyzos SA, Perakakis N, Thakkar B, Paschou SA, Katsiki N, et al. Pharmacotherapy of type 2 diabetes: an update. Metabolism. 2018;78:13–42. https://doi.org/10.1016/j.metabol.2017.08.010.

    Article  CAS  PubMed  Google Scholar 

  18. Finer N. Weight loss interventions and NAFLD: optimising liver outcomes. Diabetes Obes Metab. 2021. https://doi.org/10.1111/dom.14569.

    Article  CAS  PubMed  Google Scholar 

  19. Bifari F, Manfrini R, Dei Cas M, Berra C, Siano M, Zuin M, et al. Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Pharmacol Res. 2018;137:219–29. https://doi.org/10.1016/j.phrs.2018.09.025.

    Article  CAS  PubMed  Google Scholar 

  20. Somm E, Montandon SA, Loizides-Mangold U, Gaïa N, Lazarevic V, De Vito C, et al. The GLP-1R agonist liraglutide limits hepatic lipotoxicity and inflammatory response in mice fed a methionine-choline deficient diet. Transl Res. 2021;227:75–88. https://doi.org/10.1016/j.trsl.2020.07.008.

    Article  CAS  PubMed  Google Scholar 

  21. Polyzos SA, Kountouras J, Zavos C, Deretzi G. Nonalcoholic fatty liver disease: multimodal treatment options for a pathogenetically multiple-hit disease. J Clin Gastroenterol. 2012;46:272–84. https://doi.org/10.1097/MCG.0b013e31824587e0.

    Article  PubMed  Google Scholar 

  22. Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679–90. https://doi.org/10.1016/S0140-6736(15)00803-X.

    Article  CAS  PubMed  Google Scholar 

  23. Bajaj HS, Brown RE, Bhullar L, Sohi N, Kalra S, Aronson R. SGLT2 inhibitors and incretin agents: associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab. 2018;44:493–9. https://doi.org/10.1016/j.diabet.2018.08.001.

    Article  CAS  PubMed  Google Scholar 

  24. Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113–24. https://doi.org/10.1056/NEJMoa2028395.

    Article  CAS  PubMed  Google Scholar 

  25. Flint A, Andersen G, Hockings P, Johansson L, Morsing A, Sundby Palle M, et al. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2021;54:1150–61. https://doi.org/10.1111/apt.16608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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;105:2707–9. https://doi.org/10.1038/ajg.2010.363.

    Article  PubMed  Google Scholar 

  27. Kuchay MS, Krishan S, Mishra SK, Choudhary NS, Singh MK, Wasir JS, et al. Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial). Diabetologia. 2020;63:2434–45. https://doi.org/10.1007/s00125-020-05265-7.

    Article  CAS  PubMed  Google Scholar 

  28. Gluud LL, Knop FK, Vilsboll T. Effects of lixisenatide on elevated liver transaminases: systematic review with individual patient data meta-analysis of randomised controlled trials on patients with type 2 diabetes. BMJ Open. 2014;4: e005325. https://doi.org/10.1136/bmjopen-2014-005325.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ghosal S, Datta D, Sinha B. A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D). Sci Rep. 2021;11:22063. https://doi.org/10.1038/s41598-021-01663-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carbone LJ, Angus PW, Yeomans ND. Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31:23–31. https://doi.org/10.1111/jgh.13026.

    Article  CAS  PubMed  Google Scholar 

  31. Mantovani A, Petracca G, Beatrice G, Csermely A, Lonardo A, Targher G. Glucagon-like peptide-1 receptor agonists for treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: an updated meta-analysis of randomized controlled trials. Metabolites. 2021;11. https://doi.org/10.3390/metabo11020073.

  32. Huang YZ, Yang GY, Wang C, Chen XY, Zhang LL. Effectiveness of drug interventions in nonalcoholic fatty liver disease: a network meta-analysis. World J Diabetes. 2021;12:1576–86. https://doi.org/10.4239/wjd.v12.i9.1576.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Napoli R, Avogaro A, Formoso G, Piro S, Purrello F, Targher G, et al. Beneficial effects of glucagon-like peptide 1 receptor agonists on glucose control, cardiovascular risk profile, and non-alcoholic fatty liver disease. An expert opinion of the Italian diabetes society. Nutr Metab Cardiovasc Dis. 2021;31:3257–70. https://doi.org/10.1016/j.numecd.2021.08.039.

  34. Monami M, Nreu B, Scatena A, Cresci B, Andreozzi F, Sesti G, et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials. Diabetes Obes Metab. 2017;19:1233–41. https://doi.org/10.1111/dom.12926.

    Article  CAS  PubMed  Google Scholar 

  35. Makri E, Kita M, Goulas A, Papaioannidou P, Efstathiadou ZA, Adamidou F, et al. Comparative effectiveness of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on noninvasive indices of hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus. Diabetes Metab Syndr. 2020;14:1913–9. https://doi.org/10.1016/j.dsx.2020.09.030.

    Article  PubMed  Google Scholar 

  36. Kumar J, Memon RS, Shahid I, Rizwan T, Zaman M, Menezes RG, et al. Antidiabetic drugs and non-alcoholic fatty liver disease: a systematic review, meta-analysis and evidence map. Dig Liver Dis. 2021;53:44–51. https://doi.org/10.1016/j.dld.2020.08.021.

    Article  CAS  PubMed  Google Scholar 

  37. Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther. 2004;20:623–8. https://doi.org/10.1111/j.1365-2036.2004.02153.x.

    Article  CAS  PubMed  Google Scholar 

  38. Assy N, Hussein O, Abassi Z. Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obese patients with non-alcoholic steatohepatitis. Gut. 2007;56:443–4. https://doi.org/10.1136/gut.2006.106021.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology. 2009;49:80–6.

    Article  CAS  PubMed  Google Scholar 

  40. Wang H, Wang L, Cheng Y, Xia Z, Liao Y, Cao J. Efficacy of orlistat in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2018;9:90–6. https://doi.org/10.3892/br.2018.1100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008;31:53–65.

    Article  CAS  PubMed  Google Scholar 

  42. Bajaj HS, Burrows M, Blavignac J, Paron E, Camacho F, Gould E, et al. Extended-release naltrexone/bupropion and liver health: pooled, post hoc analysis from four randomized controlled trials. Diabetes Obes Metab. 2021;23:861–5. https://doi.org/10.1111/dom.14284.

    Article  CAS  PubMed  Google Scholar 

  43. Tuccinardi D, Farr OM, Upadhyay J, Oussaada SM, Mathew H, Paschou SA, et al. Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: a six-month, randomized, placebo-controlled, double-blind clinical trial. Diabetes Obes Metab. 2019;21:1487–92. https://doi.org/10.1111/dom.13655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733–94. https://doi.org/10.1152/physrev.00055.2009.

    Article  CAS  PubMed  Google Scholar 

  45. Thomas MC, Cherney DZI. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia. 2018;61:2098–107. https://doi.org/10.1007/s00125-018-4669-0.

    Article  CAS  PubMed  Google Scholar 

  46. Makri ES, Goulas A, Polyzos SA. Sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease. Eur J Pharmacol. 2021;907: 174272. https://doi.org/10.1016/j.ejphar.2021.174272.

    Article  CAS  PubMed  Google Scholar 

  47. Shimizu M, Suzuki K, Kato K, Jojima T, Iijima T, Murohisa T, et al. Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019;21:285–92. https://doi.org/10.1111/dom.13520.

    Article  CAS  PubMed  Google Scholar 

  48. Tobita H, Sato S, Miyake T, Ishihara S, Kinoshita Y. Effects of dapagliflozin on body composition and liver tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study. Curr Ther Res Clin Exp. 2017;87:13–9. https://doi.org/10.1016/j.curtheres.2017.07.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kurinami N, Sugiyama S, Yoshida A, Hieshima K, Miyamoto F, Kajiwara K, et al. Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus. Diabetes Res Clin Pract. 2018;142:254–63. https://doi.org/10.1016/j.diabres.2018.05.017.

    Article  CAS  PubMed  Google Scholar 

  50. Seko Y, Sumida Y, Sasaki K, Itoh Y, Iijima H, Hashimoto T, et al. Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials. J Gastroenterol. 2018;53:140–51. https://doi.org/10.1007/s00535-017-1364-8.

    Article  CAS  PubMed  Google Scholar 

  51. Leiter LA, Forst T, Polidori D, Balis DA, Xie J, Sha S. Effect of canagliflozin on liver function tests in patients with type 2 diabetes. Diabetes Metab. 2016;42:25–32. https://doi.org/10.1016/j.diabet.2015.10.003.

    Article  CAS  PubMed  Google Scholar 

  52. Inoue M, Hayashi A, Taguchi T, Arai R, Sasaki S, Takano K, et al. Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease. J Diabetes Investig. 2019;10:1004–11. https://doi.org/10.1111/jdi.12980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Seko Y, Nishikawa T, Umemura A, Yamaguchi K, Moriguchi M, Yasui K, et al. Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as stage 1–3 fibrosis. Diabetes Metab Syndr Obes. 2018;11:835–43. https://doi.org/10.2147/DMSO.S184767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cusi K, Bril F, Barb D, Polidori D, Sha S, Ghosh A, et al. Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab. 2019;21:812–21. https://doi.org/10.1111/dom.13584.

    Article  CAS  PubMed  Google Scholar 

  55. Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, et al. 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;41:1801–8. https://doi.org/10.2337/dc18-0165.

    Article  CAS  PubMed  Google Scholar 

  56. Sattar N, Fitchett D, Hantel S, George JT, Zinman B. Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME(R) trial. Diabetologia. 2018;61:2155–63. https://doi.org/10.1007/s00125-018-4702-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Seko Y, Sumida Y, Tanaka S, Mori K, Taketani H, Ishiba H, et al. Effect of sodium glucose cotransporter 2 inhibitor on liver function tests in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus. Hepatol Res. 2017;47:1072–8. https://doi.org/10.1111/hepr.12834.

    Article  CAS  PubMed  Google Scholar 

  58. Ito D, Shimizu S, Inoue K, Saito D, Yanagisawa M, Inukai K, et al. Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial. Diabetes Care. 2017;40:1364–72. https://doi.org/10.2337/dc17-0518.

    Article  CAS  PubMed  Google Scholar 

  59. Takase T, Nakamura A, Miyoshi H, Yamamoto C, Atsumi T. Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects. Endocr J. 2017;64:363–7. https://doi.org/10.1507/endocrj.EJ16-0295.

    Article  CAS  PubMed  Google Scholar 

  60. Takahashi H, Kessoku T, Kawanaka M, Nonaka M, Hyogo H, Fujii H, et al. Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD. Hepatol Commun. 2022;6:120–32. https://doi.org/10.1002/hep4.1696.

    Article  CAS  PubMed  Google Scholar 

  61. Shibuya T, Fushimi N, Kawai M, Yoshida Y, Hachiya H, Ito S, et al. Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: a prospective randomized controlled pilot study. Diabetes Obes Metab. 2018;20:438–42. https://doi.org/10.1111/dom.13061.

    Article  CAS  PubMed  Google Scholar 

  62. Yoneda M, Honda Y, Ogawa Y, Kessoku T, Kobayashi T, Imajo K, et al. Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial. BMJ Open Diabetes Res Care. 2021;9. https://doi.org/10.1136/bmjdrc-2020-001990.

  63. Coelho FDS, Borges-Canha M, von Hafe M, Neves JS, Vale C, Leite AR, et al. Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: a meta-analysis of randomized clinical trials. Diabetes Metab Res Rev. 2021;37: e3413. https://doi.org/10.1002/dmrr.3413.

    Article  CAS  PubMed  Google Scholar 

  64. Wong C, Yaow CYL, Ng CH, Chin YH, Low YF, Lim AYL, et al. Sodium-glucose co-transporter 2 inhibitors for non-alcoholic fatty liver disease in asian patients with type 2 diabetes: a meta-analysis. Front Endocrinol (Lausanne). 2020;11: 609135. https://doi.org/10.3389/fendo.2020.609135.

    Article  Google Scholar 

  65. Itani T, Ishihara T. Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. Obes Sci Pract. 2018;4:477–82. https://doi.org/10.1002/osp4.294.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Ohki T, Isogawa A, Toda N, Tagawa K. Effectiveness of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, as a second-line treatment for non-alcoholic fatty liver disease patients with type 2 diabetes mellitus who do not respond to incretin-based therapies including glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors. Clin Drug Investig. 2016;36:313–9. https://doi.org/10.1007/s40261-016-0383-1.

    Article  CAS  PubMed  Google Scholar 

  67. Ng CH, Lin SY, Chin YH, Lee MH, Syn N, Goh XL, et al. Anti-diabetic medications for type 2 diabetics with non-alcoholic fatty liver disease. Evidence from a network meta-analysis of randomised controlled trials. Endocr Pract. 2022;28:223–30. https://doi.org/10.1016/j.eprac.2021.09.013.

  68. Zheng C, Lin M, Chen Y, Xu H, Yan L, Dai H. Effects of sodium-glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta-analysis of randomized controlled trials. Cardiovasc Diabetol. 2021;20:83. https://doi.org/10.1186/s12933-021-01272-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism. 2018;79:64–76. https://doi.org/10.1016/j.metabol.2017.11.003.

    Article  CAS  PubMed  Google Scholar 

  70. Lin DS, Lee JK, Chen WJ. Clinical adverse events associated with sodium-glucose cotransporter 2 inhibitors: a meta-analysis involving 10 randomized clinical trials and 71 553 individuals. J Clin Endocrinol Metab. 2021;106:2133–45. https://doi.org/10.1210/clinem/dgab274.

    Article  PubMed  Google Scholar 

  71. Venetsanaki V, Karabouta Z, Polyzos SA. Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis. Eur J Pharmacol. 2019;863: 172661. https://doi.org/10.1016/j.ejphar.2019.172661.

    Article  CAS  PubMed  Google Scholar 

  72. Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145:574-82.e1. https://doi.org/10.1053/j.gastro.2013.05.042.

    Article  CAS  PubMed  Google Scholar 

  73. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65. https://doi.org/10.1016/s0140-6736(14)61933-4.

    Article  CAS  PubMed  Google Scholar 

  74. Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394:2184–96. https://doi.org/10.1016/s0140-6736(19)33041-7.

    Article  CAS  PubMed  Google Scholar 

  75. Majzoub AM, Nayfeh T, Barnard A, Munaganuru N, Dave S, Singh S, et al. Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH. Aliment Pharmacol Ther. 2021;54:880–9. https://doi.org/10.1111/apt.16583.

    Article  PubMed  Google Scholar 

  76. Polyzos SA, Kountouras J, Mantzoros CS. Obeticholic acid for the treatment of nonalcoholic steatohepatitis: expectations and concerns. Metabolism. 2020;104: 154144. https://doi.org/10.1016/j.metabol.2020.154144.

    Article  CAS  PubMed  Google Scholar 

  77. Polyzos SA, Xanthopoulos K, Kountouras J. Cilofexor for the treatment of nonalcoholic steatohepatitis. Curr Vasc Pharmacol. 2021. https://doi.org/10.2174/1570161119666211209161023.

    Article  Google Scholar 

  78. Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, et al. Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH: a phase 2 randomized controlled trial. Hepatology. 2020;72:58–71. https://doi.org/10.1002/hep.31205.

    Article  CAS  PubMed  Google Scholar 

  79. Pockros PJ, Fuchs M, Freilich B, Schiff E, Kohli A, Lawitz EJ, et al. CONTROL: a randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients. Liver Int. 2019;39:2082–93. https://doi.org/10.1111/liv.14209.

    Article  CAS  PubMed  Google Scholar 

  80. Cignarella A, Busetto L, Vettor R. Pharmacotherapy of obesity: an update. Pharmacol Res. 2021;169: 105649. https://doi.org/10.1016/j.phrs.2021.105649.

    Article  CAS  PubMed  Google Scholar 

  81. Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398:583–98. https://doi.org/10.1016/s0140-6736(21)01443-4.

    Article  CAS  PubMed  Google Scholar 

  82. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503–15. https://doi.org/10.1056/NEJMoa2107519.

    Article  PubMed  Google Scholar 

  83. Hartman ML, Sanyal AJ, Loomba R, Wilson JM, Nikooienejad A, Bray R, et al. Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care. 2020;43:1352–5. https://doi.org/10.2337/dc19-1892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Polyzos SA, Kountouras J, Zavos C, Tsiaousi E. The role of adiponectin in the pathogenesis and treatment of nonalcoholic fatty liver disease. Diabetes Obes Metab. 2010;12:365–83.

    Article  CAS  PubMed  Google Scholar 

  85. Ambery P, Parker VE, Stumvoll M, Posch MG, Heise T, Plum-Moerschel L, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018;391:2607–18. https://doi.org/10.1016/s0140-6736(18)30726-8.

    Article  CAS  PubMed  Google Scholar 

  86. Boland ML, Laker RC, Mather K, Nawrocki A, Oldham S, Boland BB, et al. Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis. Nat Metab. 2020;2:413–31. https://doi.org/10.1038/s42255-020-0209-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Nahra R, Wang T, Gadde KM, Oscarsson J, Stumvoll M, Jermutus L, et al. Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study. Diabetes Care. 2021;44:1433–42. https://doi.org/10.2337/dc20-2151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Jepsen MM, Christensen MB. Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Expert Opin Emerg Drugs. 2021;26:231–43. https://doi.org/10.1080/14728214.2021.1947240.

    Article  CAS  PubMed  Google Scholar 

  89. Polyzos SA, Kountouras J, Anastasiadis S, Doulberis M, Katsinelos P. Nonalcoholic fatty liver disease: is it time for combination treatment and a diabetes-like approach? Hepatology. 2018;68:389. https://doi.org/10.1002/hep.29897.

    Article  PubMed  Google Scholar 

  90. Polyzos SA, Mantzoros CS. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: a systematic review. Metabolism. 2016;65:1297–306. https://doi.org/10.1016/j.metabol.2016.05.013.

    Article  CAS  PubMed  Google Scholar 

  91. Nakanishi N, Hashimoto Y, Okamura T, Ohbora A, Kojima T, Hamaguchi M, et al. A weight regain of 1.5 kg or more and lack of exercise are associated with nonalcoholic fatty liver disease recurrence in men. Sci Rep. 2021;11:19992. https://doi.org/10.1038/s41598-021-99036-y.

  92. Weintraub M, Sundaresan PR, Schuster B, Averbuch M, Stein EC, Byrne L. Long-term weight control study. V (weeks 190 to 210). Follow-up of participants after cessation of medication. Clin Pharmacol Ther. 1992;51:615–8.

  93. Vachliotis I, Goulas A, Papaioannidou P, Polyzos SA. Nonalcoholic fatty liver disease: lifestyle and quality of life. Hormones (Athens). 2021. https://doi.org/10.1007/s42000-021-00339-6.

    Article  Google Scholar 

  94. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. 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;55:2005–23.

    Article  PubMed  Google Scholar 

  95. EASL–EASD–EASO. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia. 2016;59:1121–40. https://doi.org/10.1007/s00125-016-3902-y.

  96. Chitturi S, Wong VW, Chan WK, Wong GL, Wong SK, Sollano J, et al. The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-part 2: management and special groups. J Gastroenterol Hepatol. 2018;33:86–98. https://doi.org/10.1111/jgh.13856.

    Article  PubMed  Google Scholar 

  97. Heber D, Greenway FL, Kaplan LM, Livingston E, Salvador J, Still C, et al. Endocrine and nutritional management of the post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2010;95:4823–43. https://doi.org/10.1210/jc.2009-2128.

    Article  CAS  PubMed  Google Scholar 

  98. Lee Y, Doumouras AG, Yu J, Brar K, Banfield L, Gmora S, et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17:1040–60. https://doi.org/10.1016/j.cgh.2018.10.017.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Laboratory of Pharmacology, School of Medicine, Campus of Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece

    Stergios A. Polyzos & Antonis Goulas

  2. Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Dimitrios G. Goulis

  3. 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Olga Giouleme

  4. 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Georgios S. Germanidis

Authors
  1. Stergios A. Polyzos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrios G. Goulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Giouleme
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georgios S. Germanidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonis Goulas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stergios A. Polyzos.

Ethics declarations

Conflict of Interest

SAP: No conflict of interest. DGG: No conflict of interest. OG: No conflict of interest. GSG: No conflict of interest. AG: No conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. Therefore, a signed informed consent is not applied for this narrative review.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Metabolism

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Polyzos, S.A., Goulis, D.G., Giouleme, O. et al. Anti-obesity Medications for the Management of Nonalcoholic Fatty Liver Disease. Curr Obes Rep 11, 166–179 (2022). https://doi.org/10.1007/s13679-022-00474-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13679-022-00474-0

Keywords

Search

Navigation