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Experimental Diabetes Research
Volume 2012, Article ID 716404, 13 pages
http://dx.doi.org/10.1155/2012/716404
Review Article

The Role of Metformin in the Management of NAFLD

Endocrinology Unit, Department of Clinical and Experimental Medicine, University Magna Graecia of Catanzaro, Campus Universitario, Località Germaneto, Viale Europa, 88100 Catanzaro, Italy

Received 14 July 2011; Accepted 4 October 2011

Academic Editor: Konstantinos Kantartzis

Copyright © 2012 Angela Mazza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Citations to this Article [106 citations]

The following is the list of published articles that have cited the current article.

  • Rebeca Carter, Jack Marjot, Angelina Mouralidarane, Shuvra Ray, Junpei Soeda, and Jude Oben, “Non-alcoholic fatty liver disease: An important consideration in patients with CVD,” British Journal of Cardiac Nursing, vol. 7, no. 7, pp. 324–329, 2012. View at Publisher · View at Google Scholar
  • Sanjay Kalra, Ambika Gopalakrishnan Unnikrishnan, and Rakesh Sahay, “Metformin and the promise of geroprotection.,” Indian journal of endocrinology and metabolism, vol. 16, no. 4, pp. 496–8, 2012. View at Publisher · View at Google Scholar
  • Stergios A. Polyzos, Jannis Kountouras, and Christos S. Mantzoros, “Sulfated oxysterols as candidates for the treatment of nonalcoholic fatty liver disease,” Metabolism-Clinical And Experimental, vol. 61, no. 6, pp. 755–758, 2012. View at Publisher · View at Google Scholar
  • Aneta Stachowicz, Maciej Suski, Rafal Olszanecki, Jozef Madej, Krzysztof Okon, and Ryszard Korbut, “Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice treated with metformin,” Journal Of Proteomics, vol. 77, pp. 167–175, 2012. View at Publisher · View at Google Scholar
  • Carmine Finelli, and Giovanni Tarantino, “Have guidelines addressing physical activity been established in nonalcohol ic fatty liver disease?,” World Journal of Gastroenterology, vol. 18, no. 46, pp. 6790–6800, 2012. View at Publisher · View at Google Scholar
  • Sanjay Kalra, Puneet Dhamija, and Ashok K Das, “Metformin: Midlife maturity, maiden charm.,” Indian journal of endocrinology and metabolism, vol. 16, no. 6, pp. 1015–8, 2012. View at Publisher · View at Google Scholar
  • Yan Li, Lei Liu, Bin Wang, Jun Wang, and Dongfeng Chen, “Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis,” Biomedical Reports, vol. 1, no. 1, pp. 57–64, 2012. View at Publisher · View at Google Scholar
  • Arrigo F. G. Cicero, Elisa Tartagni, and Sibel Ertek, “Metformin and its clinical use: new insights for an old drug in clinical practice,” Archives Of Medical Science, vol. 8, no. 5, pp. 907–917, 2012. View at Publisher · View at Google Scholar
  • A. Zarrinpar, and R. Loomba, “Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease,” Alimentary Pharmacology & Therapeutics, vol. 36, no. 10, pp. 909–921, 2012. View at Publisher · View at Google Scholar
  • N. Fernando Carrasco, F. José Eduardo Galgani, and J. Marcela Reyes, “Síndrome de resistencia a la insulina. estudio y manejo,” Revista Médica Clínica Las Condes, vol. 24, no. 5, pp. 827–837, 2013. View at Publisher · View at Google Scholar
  • Jing Xu, Nan Li, Junhong Wang, Chunhong Zhang, Shimei Ding, Yang Jiao, and Jing Zhang, “Effect of metformin on the expression of SIRT1 and UCP2 in rat liver of type 2 diabetes mellitus and nonalcoholic fatty liver,” Journal of Central South University (Medical Sciences), vol. 38, no. 9, pp. 882–887, 2013. View at Publisher · View at Google Scholar
  • Titia E. Woudenberg-Vrenken, Laura Conde de la Rosa, Manon Buist-Homan, Klaas Nico Faber, and Han Moshage, “Metformin Protects Rat Hepatocytes against Bile Acid-Induced Apoptosis,” PLoS ONE, vol. 8, no. 8, 2013. View at Publisher · View at Google Scholar
  • Xiangxiang Shan, Yufeng Miao, Rengen Fan, Changzhi Song, Guangzhou Wu, Zhengqiang Wan, Jian Zhu, Guan Sun, Wenzhang Zha, Xiangming Mu, Guangjun Zhou, and Yan Chen, “Suppression of Grb2 expression improved hepatic steatosis, oxidative stress, and apoptosis induced by palmitic acid in vitro partly through insulin signaling alteration,” In Vitro Cellular & Developmental Biology - Animal, 2013. View at Publisher · View at Google Scholar
  • Hye-Young Seo, Mi-Kyung Kim, Yun-A Jung, Byoung Kuk Jang, Eun-Kyung Yoo, Keun-Gyu Park, and In-Kyu Lee, “Clusterin decreases hepatic SREBP-1c expression and lipid accumulation,” Endocrinology, vol. 154, no. 5, pp. 1722–1730, 2013. View at Publisher · View at Google Scholar
  • Jia Xiao, Rui Guo, Man Lung Fung, Emily C Liong, and George L Tipoe, “Therapeutic approaches to non-alcoholic fatty liver disease: past achievements and future challenges,” Hepatobiliary & Pancreatic Diseases International, vol. 12, no. 2, pp. 125–135, 2013. View at Publisher · View at Google Scholar
  • Leyuan Xu, Jin Koung Kim, Qianming Bai, Xin Zhang, Genta Kakiyama, Hae-ki Min, Arun J. Sanyal, William M. Pandak, and Shunlin Ren, “5-Cholesten-3 beta,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-I nduced Nonalcoholic Fatty Liver Disease Mouse Model,” Molecular Pharmacology, vol. 83, no. 3, pp. 648–658, 2013. View at Publisher · View at Google Scholar
  • A.J. Scheen, and N. Paquot, “Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes,” Diabetes & Metabolism, 2013. View at Publisher · View at Google Scholar
  • Barbara Fruci, Stefania Giuliano, Angela Mazza, Roberta Malaguarnera, and Antonino Belfiore, “Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment,” International Journal of Molecular Sciences, vol. 14, no. 11, pp. 22933–22966, 2013. View at Publisher · View at Google Scholar
  • Natalia Mazzella, Laura M. Ricciardi, Arianna Mazzotti, and Giulio Marchesini, “The Role of Medications for the Management of Patients with NAFLD,” Clinics in Liver Disease, 2013. View at Publisher · View at Google Scholar
  • Y.-H. Xun, Y.-J. Zhang, Q.-C. Pan, R.-C. Mao, Y.-L. Qin, H.-Y. Liu, Y.-M. Zhang, Y.-S. Yu, Z.-H. Tang, M.-J. Lu, G.-Q. Zang, and J.-M. Zhang, “Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells,” Journal of Viral Hepatitis, 2013. View at Publisher · View at Google Scholar
  • Khalid Mahmood, Muhammad Naeem, and Nasir Ali Rahimnajjad, “Metformin: The hidden chronicles of a magic drug,” European Journal of Internal Medicine, vol. 24, no. 1, pp. 20–26, 2013. View at Publisher · View at Google Scholar
  • Susan L. Samson, and Mandeep Bajaj, “Potential of incretin-based therapies for non-alcoholic fatty liver disease,” Journal of Diabetes and its Complications, 2013. View at Publisher · View at Google Scholar
  • Zhaoyi Huang, Xiaohu Xu, Fuer Lu, Nan Wang, Guang Chen, Yan Zhao, Xin Zou, Kaifu Wang, Hui Dong, and Lijun Xu, “Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, pp. 1–10, 2013. View at Publisher · View at Google Scholar
  • Zobair M. Younossi, Elzafir Elsheikh, and Linda L. Henry, “Current management of patients with nonalcoholic fatty liver disease,” Expert Review of Endocrinology and Metabolism, vol. 8, no. 6, pp. 549–558, 2013. View at Publisher · View at Google Scholar
  • Wen-Dee Chiang, Marthandam Asokan Shibu, Kuei-I Lee, Jia-Ping Wu, Fuu-Jen Tsai, Lung-Fa Pan, Chih-Yang Huang, and Wan-Teng Lin, “Lipolysis-stimulating peptide-VHVV ameliorates high fat diet induced hepatocyte apoptosis and fibrosis,” Journal of Functional Foods, 2014. View at Publisher · View at Google Scholar
  • André J. Scheen, “Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus,” Clinical Pharmacokinetics, 2014. View at Publisher · View at Google Scholar
  • Laura Pala, Valeria Barbaro, Ilaria Dicembrini, and Carlo Maria Rotella, “The therapy of insulin resistance in other diseases besides type 2 diabetes,” Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2014. View at Publisher · View at Google Scholar
  • Dharma Lindarto, “Effect of lifestyle modification and metformin on fetuin-A in metabolic syndrome,” Journal of the ASEAN Federation of Endocrine Societies, vol. 29, no. 1, pp. 48–52, 2014. View at Publisher · View at Google Scholar
  • André J Scheen, “Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease,” Expert Opinion on Drug Metabolism & Toxicology, pp. 1–19, 2014. View at Publisher · View at Google Scholar
  • Samir Rouabhia, Natasa Milic, and Ludovico Abenavoli, “Metformin in the treatment of non-alcoholic fatty liver disease: safety, efficacy and mechanism,” Expert Review of Gastroenterology & Hepatology, pp. 1–7, 2014. View at Publisher · View at Google Scholar
  • Minjie Lin, Shuiping Zhao, Li Shen, and Danyan Xu, “Potential Approaches to Ameliorate Hepatic Fat Accumulation Seen with MTP Inhibition,” Drug Safety, 2014. View at Publisher · View at Google Scholar
  • Kosuke Kaji, Hitoshi Yoshiji, Yasuhide Ikenaka, Ryuichi Noguchi, Yosuke Aihara, Akitoshi Douhara, Kei Moriya, Hideto Kawaratani, Yusaku Shirai, Junichi Yoshii, Koji Yanase, Mitsuteru Kitade, Tadashi Namisaki, and Hiroshi Fukui, “Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats,” Journal of Gastroenterology, vol. 49, no. 3, pp. 481–491, 2014. View at Publisher · View at Google Scholar
  • Katherine J. P. Schwenger, “Clinical approaches to non-alcoholic fatty liver disease,” World Journal of Gastroenterology, vol. 20, no. 7, pp. 1712–1723, 2014. View at Publisher · View at Google Scholar
  • Jan Willem Elte, “Diabetes en de lever,” Tijdschrift voor praktijkondersteuning, vol. 9, no. 6, pp. 174–177, 2014. View at Publisher · View at Google Scholar
  • Francesca Maria Trovato, Daniela Catalano, Giuseppe Musumeci, and Guglielmo M Trovato, “4Ps medicine of the fatty liver: The research model of predictive, preventive, personalized and participatory medicine-recommendations for facing obesity, fatty liver and fibrosis epidemics,” EPMA Journal, vol. 5, no. 1, 2014. View at Publisher · View at Google Scholar
  • Jia Liu, Yuan Xu, Yanjin Hu, and Guang Wang, “The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy,” Metabolism, 2014. View at Publisher · View at Google Scholar
  • Hong Ma, Chun-Hua Guo, Xiang-Jiu Yang, Hua-Dong Lu, Li-Gang Chen, Yan-Ling Huang, and Wen-Qiang Zhang, “Effects of dietary intervention versus metformin treatment on retinol binding protein 4 expressions in rats with non-alcoholic fatty liver disease,” Chinese Journal of Tissue Engineering Research, vol. 18, no. 49, pp. 8007–8014, 2014. View at Publisher · View at Google Scholar
  • Rostislav Chudnovskiy, Airlia Thompson, Kevin Tharp, Marc Hellerstein, Joseph L. Napoli, and Andreas Stahl, “Consumption of Clarified Grapefruit Juice Ameliorates High-Fat Diet Induced Insulin Resistance and Weight Gain in Mice,” Plos One, vol. 9, no. 10, 2014. View at Publisher · View at Google Scholar
  • Fang Liu, Chao Wang, Lijun Zhang, Yuqiao Xu, Lina Jang, Yu Gu, Xiangmei Cao, Xin Zhao, Jing Ye, and Qing Li, “Metformin prevents hepatic steatosis by regulating the expression of adipose differentiation-related protein,” International Journal of Molecular Medicine, vol. 33, no. 1, pp. 51–58, 2014. View at Publisher · View at Google Scholar
  • Anna Bohdanowicz-Pawlak, Agnieszka Lenarcik-Kabza, Anna Brona, Justyna Kuliczkowska-Plaksej, Lukasz Laczmanski, Urszula Zaleska-Dorobisz, and Andrzej Milewicz, “Non-alcoholic fatty liver disease in women with polycystic ovary syndrome - clinical and metabolic aspects and lipoprotein lipase gene polymorphism,” Endokrynologia Polska, vol. 65, no. 6, pp. 416–421, 2014. View at Publisher · View at Google Scholar
  • Dina L. Halegoua-De Marzio, and Jonathan M. Fenkel, “Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease,” Advances in Hepatology, vol. 2014, pp. 1–7, 2014. View at Publisher · View at Google Scholar
  • Suja Rani Sasidharan, Joshua Allan Joseph, Senthilkumar Anandakumar, Vijayabalaji Venkatesan, Chandrasekharan Nair Ariyattu Madhavan, and Amit Agarwal, “Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats,” The Scientific World Journal, vol. 2014, pp. 1–10, 2014. View at Publisher · View at Google Scholar
  • Steven T. Sparkes, Dhiren K. Patel, and Jennifer D. Goldman-Levine, “Past, present, and future research avenues for metformin: A literature review,” Journal of Pharmacy Technology, vol. 30, no. 6, pp. 227–234, 2014. View at Publisher · View at Google Scholar
  • Eleni A. Karavia, Aikaterini Hatziri, Christina Kalogeropoulou, Nikolaos I Papachristou, Eva Xepapadaki, Caterina Constantinou, Anastasios Natsos, Peristera-Ioanna Petropoulou, Shlomo Sasson, Dionysios J Papachristou, and Kyriakos E. Kypreos, “Deficiency in Apolipoprotein A-I ablates the pharmacological effects of metformin on plasma glucose homeostasis and hepatic lipid deposition,” European Journal of Pharmacology, 2015. View at Publisher · View at Google Scholar
  • Giovanni Tarantino, Vincenzo Citro, and Carmine Finelli, “Hype or reality: Should patients with metabolic syndromerelated nafld be on the hunter-gatherer (paleo) diet to decrease morbidity?,” Journal of Gastrointestinal and Liver Diseases, vol. 24, no. 3, pp. 359–368, 2015. View at Publisher · View at Google Scholar
  • Diana Roehrborn, Nina Wronkowitz, and Juergen Eckel, “DPP4 in diabetes,” Frontiers In Immunology, vol. 6, pp. 1–20, 2015. View at Publisher · View at Google Scholar
  • Melissa A. Linden, Kristi T. Lopez, Justin A. Fletcher, E. Matthew Morris, Grace M. Meers, Sameer Siddique, M. Harold Laughlin, James R. Sowers, John P. Thyfault, Jamal A. Ibdah, and R. Scott Rector, “Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats,” Applied Physiology, Nutrition, and Metabolism, pp. 1–10, 2015. View at Publisher · View at Google Scholar
  • Susan L. Samson, and Alan J. Garber, “Metformin and other biguanides: pharmacology and therapeutic usage,” International Textbook of Diabetes Mellitus, pp. 641–656, 2015. View at Publisher · View at Google Scholar
  • Laura Conde de la Rosa, Titia E. Vrenken, Manon Buist-Homan, Klaas Nico Faber, and Han Moshage, “Metformin protects primary rat hepatocytes against oxidative stress-induced apoptosis,” Pharmacology Research & Perspectives, vol. 3, no. 2, 2015. View at Publisher · View at Google Scholar
  • Dong Hun Lee, Ji Eun Hong, Hyung-Mun Yun, Chul Ju Hwang, Ju Ho Park, Sang Bae Han, Do Young Yoon, Min Jong Song, and Jin Tae Hong, “Interleukin-32β ameliorates metabolic disorder and liver damage in mice fed high-fat diet,” Obesity, 2015. View at Publisher · View at Google Scholar
  • Juan Zheng, Shih-Lung Woo, Xiang Hu, Rachel Botchlett, Lulu Chen, Yuqing Huo, and Chaodong Wu, “Metformin and metabolic diseases: a focus on hepatic aspects,” Frontiers of Medicine, 2015. View at Publisher · View at Google Scholar
  • B. Vergès, J.-M. Petit, and B. Bouillet, “Improvement of liver function tests by antidiabetic agents: The need for multidirectional analysis,” Diabetes & Metabolism, 2015. View at Publisher · View at Google Scholar
  • Paola Raquel B. de Oliveira, Cristiane A. da Costa, Graziele F. de Bem, Viviane S. C. Cordeiro, Izabelle B. Santos, Lenize C. R. M. de Carvalho, Ellen Paula S. da Conceicao, Patrcia Cristina Lisboa, Dayane T. Ognibene, Pergentino Jose C. Sousa, Gabriel R. Martins, Antonio Jorge R. da Silva, Roberto S. de Moura, and Angela C. Resende, “Euterpe oleracea Mart.-Derived Polyphenols Protect Mice from Diet-Induced Obesity and Fatty Liver by Regulating Hepatic Lipogenesis and Cholesterol Ex,” Plos One, vol. 10, no. 12, 2015. View at Publisher · View at Google Scholar
  • L.A. Leiter, T. Forst, D. Polidori, D.A. Balis, J. Xie, and S. Sha, “Effect of canagliflozin on liver function tests in patients with type 2 diabetes,” Diabetes & Metabolism, 2015. View at Publisher · View at Google Scholar
  • Gavin Hamilton, Michael S. Middleton, Elhamy R. Heba, and Claude B. Sirlinpp. 99–119, 2015. View at Publisher · View at Google Scholar
  • Hong Ma, Guo-Ping You, Fan Cui, Lu-Fang Chen, Xiang-Jiu Yang, Li-Gang Chen, Hua-Dong Lu, and Wen-Qiang Zhang, “Effects of a low-fat diet on the hepatic expression of adiponectin and its receptors in rats with NAFLD,” Annals of Hepatology, vol. 14, no. 1, pp. 108–117, 2015. View at Publisher · View at Google Scholar
  • Aparna Bhat, Giada Sebastiani, and Mamatha Bhat, “Systematic review: Preventive and therapeutic applications of metformin in liver disease,” World Journal of Hepatology, vol. 7, no. 12, pp. 1652–1659, 2015. View at Publisher · View at Google Scholar
  • Himanshu Rana, Himanshu D. Reddy, Dinesh Kumar Singh, Suraj Singh Yadav, Shubham Singhal, and Kauser Usman, “Comparative effect of insulin sensitizers and statin on metabolic profile and ultrasonographical score in non alcoholic fatty liver disease,” Journal of Clinical and Diagnostic Research, vol. 10, no. 8, pp. OC19–OC23, 2016. View at Publisher · View at Google Scholar
  • Eun Ju Bae, “DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control,” Archives of Pharmacal Research, 2016. View at Publisher · View at Google Scholar
  • Grażyna Wójcicka, Anna Jamroz-Wiśniewska, Grażyna Czechowska, Agnieszka Korolczuk, Sebastian Marciniak, and Jerzy Bełtowski, “The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats,” European Journal of Pharmacology, 2016. View at Publisher · View at Google Scholar
  • Moyra B. Lemus, Minh Deo, Jeffrey S. Davies, Bruce E. Kemp, John D. Elsworth, Jacqueline A. Bayliss, Vanessa V. Santos, and Zane B. Andrews, “Metformin prevents nigrostriatal dopamine degeneration independent of AMPK activation in dopamine neurons,” PLoS ONE, vol. 11, no. 7, 2016. View at Publisher · View at Google Scholar
  • Wen-Dee Chiang, Chih Yang Huang, Catherine Reena Paul, Zong-Yan Lee, and Wan-Teng Lin, “Lipolysis stimulating peptides of potato protein hydrolysate effectively suppresses high-fat-diet-induced hepatocyte apoptosis and fibrosis in aging rats,” Food & Nutrition Research, vol. 60, no. 0, 2016. View at Publisher · View at Google Scholar
  • Gregor Lorbek, Žiga Urlep, and Damjana Rozman, “Pharmacogenomic and personalized approaches to tackle the nonalcoholic fatty liver disease,” Pharmacogenomics, 2016. View at Publisher · View at Google Scholar
  • Nobuyuki Itoh, Yoshiaki Nakayama, and Morichika Konishi, “Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease,” Frontiers in Cell and Developmental Biology, vol. 4, 2016. View at Publisher · View at Google Scholar
  • Asad Dajani, and Adnan AbuHammour, “Treatment of nonalcoholic fatty liver disease: Where do we stand an overview,” Saudi Journal Of Gastroenterology, vol. 22, no. 2, pp. 91–105, 2016. View at Publisher · View at Google Scholar
  • Zhenwei Gong, Emir Tas, Shoshana Yakar, and Radhika Muzumdar, “Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging,” Molecular and Cellular Endocrinology, 2016. View at Publisher · View at Google Scholar
  • Sudhakara Gujjala, Mallaiah Putakala, Rajendran Ramaswamy, and Saralakumari Desireddy, “Preventive effect of Caralluma fimbriata vs. Metformin against high-fat diet-induced alterations in lipid metabolism in Wistar rats,” Biomedicine & Pharmacotherapy, vol. 84, pp. 215–223, 2016. View at Publisher · View at Google Scholar
  • Jessica K. Paulus, Christina D. Williams, Furha I. Cossor, Michael J. Kelley, and Robert E. Martell, “Metformin, diabetes, and survival among U.S. veterans with colorectal cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 10, pp. 1418–1425, 2016. View at Publisher · View at Google Scholar
  • Rebeca Reyes-García, Pedro Rozas-Moreno, Camilo Julio Llamoza-Torres, and Pedro Mezquita-Raya, “Hígado graso no alcohólico y diabetes,” Medicina Clínica, 2016. View at Publisher · View at Google Scholar
  • Eric M. Desjardins, James S. Lally, Rebecca J. Ford, Brennan K. Smith, Katarina Marcinko, and Gregory R. Steinberg, “Treatment of nonalcoholic fatty liver disease: Role of AMPK,” American Journal of Physiology - Endocrinology and Metabolism, vol. 311, no. 4, pp. E730–E740, 2016. View at Publisher · View at Google Scholar
  • Newaz Hossain, Pushpjeet Kanwar, and Smruti R. Mohanty, “A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD,” Gastroenterology Research and Practice, vol. 2016, pp. 1–17, 2016. View at Publisher · View at Google Scholar
  • Sh. Zulnoorian, Almasi, Keshvarz, Shahebrahimi, Sharifi, and Farshchian, “A comparison of the therapeutic effects of metformin, pioglitazone and vitamin E in patients with non-alcoholic fatty liver,” Journal of Babol University of Medical Sciences, vol. 19, no. 9, pp. 32–38, 2017. View at Publisher · View at Google Scholar
  • Izabelle Barcellos Santos, Graziele Freitas de Bem, Viviane Silva Cristino Cordeiro, Cristiane Aguiar da Costa, Lenize Costa Reis Marins de Carvalho, Ana Paula Machado da Rocha, Gisele França da Costa, Dayane Teixeira Ognibene, Roberto Soares de Moura, and Angela Castro Resende, “Supplementation with Vitis vinifera L. skin extract improves insulin resistance and prevents hepatic lipid accumulation and steatosis in high-fat diet-fed mice,” Nutrition Research, 2017. View at Publisher · View at Google Scholar
  • Kelley G. Núñez, Janet Gonzalez-Rosario, Paul T. Thevenot, and Ari J. Cohen, “Cyclin D1 in the liver: Role of noncanonical signaling in liver steatosis and hormone regulation,” Ochsner Journal, vol. 17, no. 1, pp. 56–65, 2017. View at Publisher · View at Google Scholar
  • Kunal Maniar, Amal Moideen, Amol Patil, Ankur Mittal, Amitava Chakrabarti, and Dibyajyoti Banerjee, “A story of metformin-butyrate synergism to control various pathological conditions as a consequence of gut microbiome modification: Genesis of a wonder drug?,” Pharmacological Research, vol. 117, pp. 103–128, 2017. View at Publisher · View at Google Scholar
  • David F. Ackart, Michael A. Richardson, Brendan K. Podell, James E. DiLisio, Bruce Pulford, and Randall J. Basaraba, “A model of type 2 diabetes in the Guinea pig using sequential dietinduced glucose intolerance and streptozotocin treatment,” DMM Disease Models and Mechanisms, vol. 10, no. 2, pp. 151–162, 2017. View at Publisher · View at Google Scholar
  • Rebeca Reyes-García, Pedro Rozas-Moreno, Camilo Julio Llamoza-Torres, and Pedro Mezquita-Raya, “Non-alcoholic fatty liver disease and diabetes,” Medicina Clínica (English Edition), 2017. View at Publisher · View at Google Scholar
  • Elizabeth P. Mills, K. Paige D. Brown, Jennifer D. Smith, Phillip W. Vang, and Katie Trotta, “Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety,” Therapeutic Advances in Endocrinology and Metabolism, pp. 204201881774185, 2017. View at Publisher · View at Google Scholar
  • Merilin Al Sharif, Petko Alov, Vessela Vitcheva, Antonia Diukendjieva, Mattia Mori, Bruno Botta, Ivanka Tsakovska, and Ilza Pajeva, “Natural modulators of nonalcoholic fatty liver disease: Mode of action analysis and in silico ADME-Tox prediction,” Toxicology and Applied Pharmacology, vol. 337, pp. 45–66, 2017. View at Publisher · View at Google Scholar
  • Christopher H. Scott, Kuan-Minn Cha, Jason Ngai, Changtao Jiang, Kim Cheng, Rebecca A. Stokes, Kenneth W. K. Ho, Jacob George, Frank J. Gonzalez, and Jenny E. Gunton, “Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) regulates metabolism in mice,” Plos One, vol. 12, no. 11, pp. e0186543, 2017. View at Publisher · View at Google Scholar
  • Yoshihito Fujita, and Nobuya Inagaki, “Metformin: New Preparations and Nonglycemic Benefits,” Current Diabetes Reports, vol. 17, no. 1, 2017. View at Publisher · View at Google Scholar
  • Min-Jie Lin, Wen Dai, Rong Li, Yi-Qi Zhang, Yang Yang, Xian-Sheng Huang, Melanie J. Scott, and Lu-Zhu Chen, “Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRa signaling pathway,” Oncotarget, vol. 8, no. 65, pp. 108802–108809, 2017. View at Publisher · View at Google Scholar
  • Biyu Hou, Yuerong Zhao, Guifen Qiang, Xiuying Yang, Chunyang Xu, Xi Chen, Chenge Liu, Xiaobo Wang, Li Zhang, and Guanhua Du, “ Puerarin Mitigates Diabetic Hepatic Steatosis and Fibrosis by Inhibiting TGF- β Signaling Pathway Activation in Type 2 Diabetic Rats ,” Oxidative Medicine and Cellular Longevity, vol. 2018, pp. 1–13, 2018. View at Publisher · View at Google Scholar
  • Xiaopeng Zhu, Hongmei Yan, Mingfeng Xia, Xinxia Chang, Xi Xu, Liu Wang, Xiaoyang Sun, Yan Lu, Hua Bian, Xiaoying Li, and Xin Gao, “Metformin attenuates triglyceride accumulation in HepG2 cells through decreasing stearyl-coenzyme A desaturase 1 expression,” Lipids in Health and Disease, vol. 17, no. 1, 2018. View at Publisher · View at Google Scholar
  • Hui-Hua Chang, Aune Moro, Caroline Ei Ne Chou, David W. Dawson, Samuel French, Andrea I. Schmidt, James Sinnett-Smith, Fang Hao, O. Joe Hines, Guido Eibl, and Enrique Rozengurt, “Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model,” Scientific Reports, vol. 8, no. 1, 2018. View at Publisher · View at Google Scholar
  • Cristina Bianchi, Giuseppe Daniele, Angela Dardano, and Stefano Del Prato, “Treatment with Oral Drugs,” Diabetes. Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment, pp. 1–44, 2018. View at Publisher · View at Google Scholar
  • Elena Piccinin, Gaetano Villani, and Antonio Moschetta, “Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators,” Nature Reviews Gastroenterology & Hepatology, 2018. View at Publisher · View at Google Scholar
  • Jiajing Zhao, Yingjue Wang, Xi Wu, Ping Tong, Shurong Gao, Dongping Huang, Jianwei Huang, and Yaohan Yue, “Inhibition of CCL19 benefits non‑alcoholic fatty liver disease by inhibiting TLR4/NF‑κB‑p65 signaling,” Molecular Medicine Reports, vol. 18, no. 5, pp. 4635–4642, 2018. View at Publisher · View at Google Scholar
  • Cristina Bianchi, Giuseppe Daniele, Angela Dardano, and Stefano Del Prato, “Treatment with Oral Drugs,” Diabetes Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment, pp. 527–569, 2018. View at Publisher · View at Google Scholar
  • Gabriela Handzlik-Orlik, Michał Holecki, Joanna Kozaczka, Michał Kukla, Katarzyna Wyskida, Leszek Kędzierski, Krzysztof Pawlicki, and Jan Duława, “Evaluation of metformin therapy using controlled attenuation parameter and transient elastography in patients with non-alcoholic fatty liver disease,” Pharmacological Reports, 2018. View at Publisher · View at Google Scholar
  • Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, and Marc Foretz, “AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development,” EBioMedicine, 2018. View at Publisher · View at Google Scholar
  • Hong-Jun Chen, and Jin Liu, “Actein ameliorates hepatic steatosis and fibrosis in high fat diet-induced NAFLD by regulation of insulin and leptin resistant,” Biomedicine and Pharmacotherapy, vol. 97, pp. 1386–1396, 2018. View at Publisher · View at Google Scholar
  • Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, and Bo-Yeon Kim, “Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease,” Endocrinology and Metabolism, vol. 33, no. 3, pp. 387, 2018. View at Publisher · View at Google Scholar
  • Hyekyung Yang, and Cheol-Young Park, “Glucose-Lowering Agents in the Management of Nonalcoholic Fatty Liver Disease,” The Journal of Korean Diabetes, vol. 19, no. 2, pp. 88, 2018. View at Publisher · View at Google Scholar
  • Fengxia Zhang, Shizhan Ma, Wenxiu Sun, Jianbo Chen, Lusheng Jiang, Ping Yang, Yufang Huang, Aihua Gong, and Shudong Liu, “SREBP-2, a new target of metformin?,” Drug Design, Development and Therapy, vol. 12, pp. 4163–4170, 2018. View at Publisher · View at Google Scholar
  • Adriana Fontes, Mireia Alemany-Pagès, Paulo J. Oliveira, João Ramalho-Santos, Hans Zischka, and Anabela Marisa Azul, “Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease,” International Journal of Molecular Sciences, vol. 20, no. 16, pp. 3987, 2019. View at Publisher · View at Google Scholar
  • Marc Foretz, Bruno Guigas, and Benoit Viollet, “Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus,” Nature Reviews Endocrinology, 2019. View at Publisher · View at Google Scholar
  • Kyong Kim, Gong Deuk Bae, Minho Lee, Eun-Young Park, Dong Jae Baek, Chul Young Kim, Hee-Sook Jun, and Yoon Sin Oh, “Allomyrina dichotoma Larva Extract Ameliorates the Hepatic Insulin Resistance of High-Fat Diet-Induced Diabetic Mice,” Nutrients, vol. 11, no. 7, pp. 1522, 2019. View at Publisher · View at Google Scholar
  • Melissa A. Linden, Trenton T. Ross, David A. Beebe, Matthew F. Gorgoglione, Karyn L. Hamilton, Benjamin F. Miller, Barry Braun, and William P. Esler, “Interaction between an SGLT2 inhibitor and exercise training,” Metabolism, 2019. View at Publisher · View at Google Scholar
  • Gavin Hamilton, Michael S. Middleton, Elhamy R. Heba, and Claude B. Sirlin, “Non-invasive Quantitative Magnetic Resonance Imaging and Spectroscopic Biomarkers in Nonalcoholic Fatty Liver Disease and Other Cardiometabolic Diseases Associated with Ectopic Fat Deposition,” Translational Research Methods in Diabetes, Obesity, and Nonalcoholic Fatty Liver Disease, pp. 141–160, 2019. View at Publisher · View at Google Scholar
  • Alicia Bort, Belén Sánchez, Pedro Mateos-Gómez, Inés Díaz-Laviada, and Nieves Rodríguez-Henche, “Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation,” International Journal of Molecular Sciences, vol. 20, no. 7, pp. 1660, 2019. View at Publisher · View at Google Scholar
  • Marit Espe, Shiwei Xie, Shijun Chen, Araujo Pedro, and Elisabeth Holen, “Development of a fatty liver model using oleic acid in primary liver cells isolated from Atlantic salmon and the prevention of lipid accumulation using metformin,” Aquaculture Nutrition, 2019. View at Publisher · View at Google Scholar
  • Shazia Hussain, and Tahseen A. Chowdhury, “The Impact of Comorbidities on the Pharmacological Management of Type 2 Diabetes Mellitus,” Drugs, 2019. View at Publisher · View at Google Scholar
  • Yamei Han, Chun Wei, Jing Fang, Jian-Gao Fan, Yu Li, Zhimin Hu, Feifei Zhang, Yanyan Yu, Jing Gao, Jingya Li, Jia Li, Bao-Liang Song, Aoyuan Cui, Zhengshuai Liu, Fengguang Ma, Yaqian Xue, Yuxiao Liu, and Zehua Zhao, “Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene,” Nature Communications, vol. 10, no. 1, 2019. View at Publisher · View at Google Scholar
  • Wenjing Zai, Wei Chen, Zimei Wu, Xin Jin, Jiajun Fan, Xuyao Zhang, Jingyun Luan, Shijie Tang, Xiaobin Mei, Qiang Hao, Hongrui Liu, and Dianwen Ju, “Targeted Interleukin-22 Gene Delivery in the Liver by Polymetformin and Penetratin-Based Hybrid Nanoparticles to Treat Nonalcoholic Fatty Liver Disease,” ACS Applied Materials & Interfaces, 2019. View at Publisher · View at Google Scholar
  • Shima A. Dowla, Amy M. Goss, and Ambika P. Ashraf, “Nonalcoholic Fatty Liver Disease in Children with Obesity,” Global Perspectives on Childhood Obesity, pp. 255–268, 2019. View at Publisher · View at Google Scholar