metformin and Fatty Liver studies

Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.

Fatty Liver: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.

Research Excerpts

Excerpt	Relevance	Reference
"Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD."	9.17	Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. ( Fan, H; Pan, Q; Xu, Y; Yang, X, 2013)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."	9.15	Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
"The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated."	9.14	Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. ( Ehlers, LB; Love-Osborne, K; Nadeau, KJ; Zeitler, PS, 2009)
"No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation."	9.14	Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. ( Birkeland, K; Bjøro, K; Eggesbø, HB; Haaland, T; Haukeland, JW; Konopski, Z; Løberg, EM; Raschpichler, G; von Volkmann, HL, 2009)
"Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated."	9.11	A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. ( Bugianesi, E; David, E; Gentilcore, E; Manini, R; Marchesini, G; Natale, S; Rizzetto, M; Vanni, E; Villanova, N, 2005)
"To examine the effect of metformin treatment during ischemia/reperfusion injury in fatty liver and determine the possible mechanisms."	7.96	Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB Axis ( Huang, C; Li, X; Wang, L; Yang, X, 2020)
"Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders."	7.91	Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota. ( Adeshirlarijaney, A; Chassaing, B; Gewirtz, AT; Tran, HQ; Zou, J, 2019)
" This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high-fat diet fed type 1 diabetic mice by comparison with metformin."	7.85	Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice. ( Cho, HW; Choi, MS; Choi, RY; Ham, JR; Kim, MJ; Lee, HI; Lee, J; Lee, MK; Park, SK; Seo, KI, 2017)
"We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats."	7.83	Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver. ( Hsieh, PS; Hung, YJ; Lu, CH, 2016)
" To better understand the pathophysiology of obesity-associated NAFLD, the present study examined the involvement of liver and adipose tissues in metformin actions on reducing hepatic steatosis and inflammation during obesity."	7.80	Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. ( An, X; Botchlett, R; Chen, L; Guo, T; Guo, X; Hu, X; Huo, Y; Li, H; Li, Q; Pei, Y; Qi, T; Woo, SL; Wu, C; Xiao, X; Xu, H; Xu, Y; Zhao, J; Zhao, Y; Zheng, J, 2014)
"To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet."	7.77	[Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes]. ( Fu, JF; Huang, Y; Liu, LR; Shi, HB, 2011)
" Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study."	7.77	Therapeutic effect of metformin and vitamin E versus prescriptive diet in obese adolescents with fatty liver. ( Akcam, M; Boyaci, A; Dundar, BN; Kaya, S; Pirgon, O; Uysal, S, 2011)
"To report a case of idiosyncratic hepatotoxicity associated with metformin in the treatment of type 2 diabetes with nonalcoholic fatty liver disease (NAFLD)."	7.76	Hepatotoxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease. ( Bachyrycz, AM; Cone, CJ; Murata, GH, 2010)
"Our aim was to evaluate effects of metformin, rosiglitazone, and diet with exercise in nonalcoholic fatty liver disease."	7.74	The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic fatty liver disease. ( Aksoy, N; Akyüz, F; Beşişik, F; Boztaş, G; Cakaloğlu, Y; Cevikbaş, U; Demir, K; Ibrişim, D; Kaymakoğlu, S; Mungan, Z; Okten, A; Ozdil, S; Poturoğlu, S, 2007)
"A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR)."	7.74	Effect of metformin and rosiglitazone in a prepubertal boy with Alström syndrome. ( Anhalt, H; Bhangoo, A; Collin, GB; Maclaren, N; Marshall, JD; Naggert, JK; Sinha, SK; Ten, S, 2007)
"To explore the therapeutic effects of metformin on rat fatty livers induced by high fat feeding."	7.73	[Study on therapeutic effects of metformin on rat fatty livers induced by high fat feeding]. ( Dong, H; Gao, ZQ; Lu, FE; Wang, KF; Xu, LJ; Zhou, X, 2005)
"To investigate the effects of metformin on fatty livers in insulin-resistant rats."	7.73	[Effects of metformin on fatty liver in insulin-resistant rats]. ( Chen, SQ; Deng, JC; Liu, Q; Sun, H; Tang, L, 2005)
"To assess whether treatment with insulin-sensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD)."	7.73	Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease. ( Assy, N; Bersudsky, I; Grozovski, M; Hussein, O; Szvalb, S, 2006)
"Metformin treatment was associated with significant decrease in PWV and AI in NAFLD patients."	6.76	Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. ( Boaz, M; Mashavi, M; Matas, Z; Shargorodsky, M; Sofer, E, 2011)
" Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks."	6.76	Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. ( Abrams, SH; Brunt, EM; Chalasani, N; Clark, JM; Hoofnagle, JH; Kleiner, DE; Lavine, JE; Molleston, JP; Murray, KF; Robuck, PR; Rosenthal, P; Sanyal, AJ; Scheimann, AO; Schwimmer, JB; Tonascia, J; Ünalp, A; Van Natta, ML, 2011)
"Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD)."	6.74	The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. ( Gedik, O; Nar, A, 2009)
"Metformin is an antidiabetic drug used widely in clinical practice."	6.48	Mechanisms involved in the protective effects of metformin against nonalcoholic fatty liver disease. ( Barbero-Becerra, VJ; Chavez-Tapia, NC; Mendez-Sanchez, N; Santiago-Hernandez, JJ; Uribe, M; Villegas-Lopez, FA, 2012)
"Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan."	6.43	[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance]. ( Kawaguchi, K; Korenaga, K; Korenaga, M; Sakaida, I; Uchida, K, 2006)
"Metformin alone reduced hyperinsulinemia and circulating c-reactive protein, but exacerbated nephropathy."	5.72	Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice. ( Calcutt, NA; Doty, R; Flurkey, K; Harrison, DE; Koza, RA; Reifsnyder, PC, 2022)
"Metformin is increasingly used to treat gestational diabetes (GDM) and pregnancies complicated by pregestational type 2 diabetes or polycystic ovary syndrome but data regarding long-term offspring outcome are lacking in both human studies and animal models."	5.72	Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring. ( Aiken, CE; Ashmore, TJ; Blackmore, HL; Dearden, L; Fernandez-Twinn, DS; Ozanne, SE; Pantaleão, LC; Pellegrini Pisani, L; Schoonejans, JM; Tadross, JA, 2022)
"Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice."	5.43	Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21. ( Byun, JK; Cho, ML; Choi, JY; Jeong, JH; Jhun, JY; Kim, EK; Kim, JK; Lee, SH; Lee, SY, 2016)
"Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes."	5.38	Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis. ( Ando, H; Fujimura, A; Hayashi, K; Kaneko, S; Kato, K; Kimura, T; Kita, Y; Kurita, S; Matsuzawa-Nagata, N; Misu, H; Miyamoto, K; Nakanuma, Y; Ni, Y; Ota, T; Otoda, T; Takamura, T; Takeshita, Y; Uno, M; Zen, Y, 2012)
"There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease."	5.31	Metformin reverses fatty liver disease in obese, leptin-deficient mice. ( Chuckaree, C; Diehl, AM; Kuhajda, F; Lin, HZ; Ronnet, G; Yang, SQ, 2000)
"Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD."	5.17	Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. ( Fan, H; Pan, Q; Xu, Y; Yang, X, 2013)
" Weight, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), insulin, total and direct bilirubin, fasting blood sugar (FBS), glycated hemoglobin (HbA1c), uric acid, albumin and lipid profile were evaluated at baseline and at the end of trial."	5.16	Investigation of the effects of Chlorella vulgaris supplementation in patients with non-alcoholic fatty liver disease: a randomized clinical trial. ( Beiraghdar, F; Ghamarchehreh, ME; Jalalian, HR; Panahi, Y; Sahebkar, A; Zare, R, 2012)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."	5.15	Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
"The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated."	5.14	Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. ( Ehlers, LB; Love-Osborne, K; Nadeau, KJ; Zeitler, PS, 2009)
"Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH."	5.14	Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. ( Borg, BB; Feld, JJ; Hoofnagle, JH; Kleiner, DE; Liang, TJ; Loomba, R; Lutchman, G; Modi, A; Nagabhyru, P; Ricks, M; Sumner, AE, 2009)
"No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation."	5.14	Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. ( Birkeland, K; Bjøro, K; Eggesbø, HB; Haaland, T; Haukeland, JW; Konopski, Z; Løberg, EM; Raschpichler, G; von Volkmann, HL, 2009)
"In our 6-month prospective study, both low-dose metformin and dietary treatment alone ameliorated liver steatosis and metabolic derangements in patients with NAFLD."	5.14	Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study. ( Abenavoli, L; Abenavoli, S; Belfiore, A; De Siena, M; Fruci, B; Garinis, GA; Greco, M; Gulletta, E; Mazza, A; Ventura, V, 2010)
"Previous studies demonstrated that in experimental animals fatty liver is associated with reduced hepatic blood flow and that metformin reverses steatosis, while no data were reported in humans."	5.11	Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological treatment. A pilot study. ( Berzigotti, A; Bianchi, G; Magalotti, D; Marchesini, G; Ramilli, S; Zoli, M, 2004)
"Open-label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life."	5.11	A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. ( Deutsch, R; Lavine, JE; Middleton, MS; Schwimmer, JB, 2005)
"Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated."	5.11	A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. ( Bugianesi, E; David, E; Gentilcore, E; Manini, R; Marchesini, G; Natale, S; Rizzetto, M; Vanni, E; Villanova, N, 2005)
"A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery."	4.90	Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets. ( Henry, L; Mehta, R; Mishra, A; Reyes, MJ; Younossi, ZM, 2014)
"Metformin is a widely used and extensively studied insulin sensitising drug for the treatment of women with polycystic ovary syndrome (PCOS), with various actions in tissues responding to insulin that include the liver, skeletal muscle, adipose tissue, the endothelium of blood vessels, and the ovaries."	4.88	Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient: the role of metformin. ( Hodges, P; Randeva, HS; Tan, BK; Weickert, MO, 2012)
" Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes patients known to partially attenuate fatty liver, reduces the infection of human and hACE2 hepatocytes."	4.12	The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes. ( Azkargorta, M; Bravo, M; Delgado, TC; Egia-Mendikute, L; Eguileor Giné, A; Elortza, F; Ereño-Orbea, J; Gil-Pitarch, C; Goikoetxea-Usandizaga, N; González-Recio, I; Jiménez-Barbero, J; Jover, R; Lachiondo-Ortega, S; Lee, SY; Martínez-Chantar, ML; Martínez-Cruz, LA; Mercado-Gómez, M; Nogueiras, R; Palazon, A; Petrov, P; Prevot, V; Prieto-Fernández, E; Rodríguez-Agudo, R; Serrano-Maciá, M; Simón, J; Vila-Vecilla, L, 2022)
"To examine the effect of metformin treatment during ischemia/reperfusion injury in fatty liver and determine the possible mechanisms."	3.96	Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB Axis ( Huang, C; Li, X; Wang, L; Yang, X, 2020)
"Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders."	3.91	Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota. ( Adeshirlarijaney, A; Chassaing, B; Gewirtz, AT; Tran, HQ; Zou, J, 2019)
"Co-treatment with T317 and metformin inhibited the development of atherosclerosis without activation of lipogenesis, suggesting that combined treatment with T317 and metformin may be a novel approach to inhibition of atherosclerosis."	3.88	Functional interplay between liver X receptor and AMP-activated protein kinase α inhibits atherosclerosis in apolipoprotein E-deficient mice - a new anti-atherogenic strategy. ( Chen, Y; Duan, Y; Feng, K; Han, J; Hu, W; Li, L; Li, X; Liu, L; Liu, Y; Ma, C; Miao, RQ; Sun, L; Yang, J; Yang, S; Yang, X; Yu, M; Zhang, W; Zhang, X; Zhu, Y, 2018)
" We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis."	3.88	Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model. ( Belloni, L; Blandino, G; Di Cocco, S; Guerrieri, F; Levrero, M; Marra, F; Mori, F; Nunn, ADG; Pallocca, M; Pediconi, N; Piconese, S; Pulito, C; Sacconi, A; Salerno, D; Strano, S; Testoni, B; Vivoli, E, 2018)
"The present study aimed to investigate the effect of metformin on the induction of autophagy in the liver and adipose tissues of a mouse model of obesity."	3.85	Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. ( Li, M; Sharma, A; Tan, X; Xiao, Y; Yin, C, 2017)
" This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high-fat diet fed type 1 diabetic mice by comparison with metformin."	3.85	Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice. ( Cho, HW; Choi, MS; Choi, RY; Ham, JR; Kim, MJ; Lee, HI; Lee, J; Lee, MK; Park, SK; Seo, KI, 2017)
"In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD)."	3.83	Metformin increases hepatic leptin receptor and decreases steatosis in mice. ( Cui, Y; Gan, L; Li, J; Tang, X; Wang, X; Xiang, W; Xie, B; Xu, Z, 2016)
"We investigated the effects of metformin and celecoxib on obesity-induced adipose tissue inflammation, insulin resistance (IR), fatty liver, and high blood pressure in high-fat (HF) fed rats."	3.83	Additional effect of metformin and celecoxib against lipid dysregulation and adipose tissue inflammation in high-fat fed rats with insulin resistance and fatty liver. ( Hsieh, PS; Hung, YJ; Lu, CH, 2016)
"Here, we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats."	3.80	Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats. ( Booth, FW; Crissey, JM; Fletcher, JA; Ibdah, JA; Kearney, ML; Laughlin, MH; Linden, MA; Meers, GM; Morris, EM; Rector, RS; Sowers, JR; Thyfault, JP, 2014)
" To better understand the pathophysiology of obesity-associated NAFLD, the present study examined the involvement of liver and adipose tissues in metformin actions on reducing hepatic steatosis and inflammation during obesity."	3.80	Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. ( An, X; Botchlett, R; Chen, L; Guo, T; Guo, X; Hu, X; Huo, Y; Li, H; Li, Q; Pei, Y; Qi, T; Woo, SL; Wu, C; Xiao, X; Xu, H; Xu, Y; Zhao, J; Zhao, Y; Zheng, J, 2014)
"The administration of a HFD induces insulin resistance in the liver sinusoidal endothelium, which is mediated, at least in part, through iNOS upregulation and can be prevented by the administration of metformin."	3.77	Insulin resistance and liver microcirculation in a rat model of early NAFLD. ( Abraldes, JG; Bosch, J; García-Pagán, JC; La Mura, V; Pasarín, M; Rodríguez-Vilarrupla, A, 2011)
"To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet."	3.77	[Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes]. ( Fu, JF; Huang, Y; Liu, LR; Shi, HB, 2011)
" Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study."	3.77	Therapeutic effect of metformin and vitamin E versus prescriptive diet in obese adolescents with fatty liver. ( Akcam, M; Boyaci, A; Dundar, BN; Kaya, S; Pirgon, O; Uysal, S, 2011)
"To report a case of idiosyncratic hepatotoxicity associated with metformin in the treatment of type 2 diabetes with nonalcoholic fatty liver disease (NAFLD)."	3.76	Hepatotoxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease. ( Bachyrycz, AM; Cone, CJ; Murata, GH, 2010)
" We followed the spontaneous evolution of liver steatosis and tested the therapeutic usefulness of metformin and fenofibrate in a model of steatosis, the Zucker diabetic fatty (ZDF) rat."	3.75	Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate. ( Abdallah, P; Basset, A; Beylot, M; del Carmine, P; Forcheron, F; Haffar, G, 2009)
"Our aim was to evaluate effects of metformin, rosiglitazone, and diet with exercise in nonalcoholic fatty liver disease."	3.74	The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic fatty liver disease. ( Aksoy, N; Akyüz, F; Beşişik, F; Boztaş, G; Cakaloğlu, Y; Cevikbaş, U; Demir, K; Ibrişim, D; Kaymakoğlu, S; Mungan, Z; Okten, A; Ozdil, S; Poturoğlu, S, 2007)
"A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR)."	3.74	Effect of metformin and rosiglitazone in a prepubertal boy with Alström syndrome. ( Anhalt, H; Bhangoo, A; Collin, GB; Maclaren, N; Marshall, JD; Naggert, JK; Sinha, SK; Ten, S, 2007)
"To explore the therapeutic effects of metformin on rat fatty livers induced by high fat feeding."	3.73	[Study on therapeutic effects of metformin on rat fatty livers induced by high fat feeding]. ( Dong, H; Gao, ZQ; Lu, FE; Wang, KF; Xu, LJ; Zhou, X, 2005)
"To investigate the effects of metformin on fatty livers in insulin-resistant rats."	3.73	[Effects of metformin on fatty liver in insulin-resistant rats]. ( Chen, SQ; Deng, JC; Liu, Q; Sun, H; Tang, L, 2005)
"To investigate the therapeutic effects of insulin-sensitizing drugs, rosiglitazone and metformin, on nonalcoholic fatty liver disease (NAFLD)."	3.73	[Therapeutic effects of insulin-sensitizing drugs on nonalcoholic fatty liver disease: experiment with rats]. ( Chen, WK; Wang, T; Zhang, DM; Zhang, GY; Zhong, HJ, 2006)
"To assess whether treatment with insulin-sensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD)."	3.73	Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease. ( Assy, N; Bersudsky, I; Grozovski, M; Hussein, O; Szvalb, S, 2006)
"In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor."	3.30	Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study. ( Kang, SM; Lim, S; Sohn, M; Yun, HM, 2023)
"Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat."	2.87	Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation. ( de Zegher, F; García Beltrán, C; Ibáñez, L; López-Bermejo, A, 2018)
"Individuals with type 2 diabetes (n = 44) and glycated hemoglobin ≤ 7."	2.80	Effect of vildagliptin on hepatic steatosis. ( Al-Mrabeh, A; Foley, JE; Hollingsworth, KG; Macauley, M; Schweizer, A; Smith, FE; Taylor, R; Thelwall, PE, 2015)
"Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin (7."	2.80	Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. ( Castel, H; Chartrand, G; Chiasson, JL; de Guise, J; Gilbert, G; Julien, AS; Massicotte-Tisluck, K; Olivié, D; Rabasa-Lhoret, R; Soulez, G; Tang, A; Wartelle-Bladou, C, 2015)
"Pioglitazone was more effective than glibenclamide in improving inflammation and hepatic steatosis indices."	2.78	Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin. ( D'Angelo, A; Derosa, G; Fogari, E; Maffioli, P; Perrone, T, 2013)
"Fetuin A levels were elevated in NAFLD."	2.77	Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. ( Aasheim, ET; Aukrust, P; Birkeland, KI; Dahl, TB; Gladhaug, IP; Haaland, T; Halvorsen, B; Haukeland, JW; Johansen, OE; Konopski, Z; Løberg, EM; Wium, C; Yndestad, A, 2012)
"Metformin treatment was associated with significant decrease in AI during one year treatment in NAFLD patients."	2.77	Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering? ( Boaz, M; Gavish, D; Matas, Z; Omelchenko, E; Shargorodsky, M, 2012)
"Patients with treatment-naive type 2 diabetes (N = 16) were treated with insulin and metformin for a 3-month lead-in period, then assigned triple oral therapy (metformin, glyburide, and pioglitazone) or continued treatment with insulin and metformin."	2.77	Effect of insulin versus triple oral therapy on the progression of hepatic steatosis in type 2 diabetes. ( Duong, J; Leonard, D; Lingvay, I; Roe, ED; Szczepaniak, LS, 2012)
"Metformin treatment was associated with significant decrease in PWV and AI in NAFLD patients."	2.76	Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. ( Boaz, M; Mashavi, M; Matas, Z; Shargorodsky, M; Sofer, E, 2011)
" Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks."	2.76	Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. ( Abrams, SH; Brunt, EM; Chalasani, N; Clark, JM; Hoofnagle, JH; Kleiner, DE; Lavine, JE; Molleston, JP; Murray, KF; Robuck, PR; Rosenthal, P; Sanyal, AJ; Scheimann, AO; Schwimmer, JB; Tonascia, J; Ünalp, A; Van Natta, ML, 2011)
"Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD)."	2.74	The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. ( Gedik, O; Nar, A, 2009)
"The increased risk of type 2 diabetes and cardiovascular disease in PCOS is closely associated with BMI."	2.55	Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review. ( Andersen, M; Glintborg, D, 2017)
"Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance."	2.50	The therapy of insulin resistance in other diseases besides type 2 diabetes. ( Barbaro, V; Dicembrini, I; Pala, L; Rotella, CM, 2014)
"Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide."	2.49	Nonalcoholic Fatty liver: a possible new target for type 2 diabetes prevention and treatment. ( Belfiore, A; Fruci, B; Giuliano, S; Malaguarnera, R; Mazza, A, 2013)
"Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH)."	2.49	Pharmacologic therapy for nonalcoholic fatty liver disease in adults. ( Bell, AM; Byrd, JS; Malinowski, SS; Riche, DM; Wofford, MR, 2013)
"Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, comprises a spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis."	2.49	Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD. ( Baldelli, E; Carulli, L; George, J; Hebbard, L; Loria, P; Maurantonio, M, 2013)
"Metformin is an antidiabetic drug used widely in clinical practice."	2.48	Mechanisms involved in the protective effects of metformin against nonalcoholic fatty liver disease. ( Barbero-Becerra, VJ; Chavez-Tapia, NC; Mendez-Sanchez, N; Santiago-Hernandez, JJ; Uribe, M; Villegas-Lopez, FA, 2012)
"Obesity is known to be the most common cause of simple steatosis in the preadolescent and adolescent population with a consequent serious health risk."	2.47	[Fatty liver and its clinical management in obese adolescents]. ( Álvarez Ferre, J; González Jiménez, E; Schmidt Río-Valle, J, 2011)
"Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease worldwide."	2.47	Nonalcoholic fatty liver disease and type 2 diabetes mellitus: the hidden epidemic. ( Ismail, MH, 2011)
"Non-alcoholic fatty liver disease (NAFLD) is closely linked with obesity and the prevalence of NAFLD is about 17% to 33% in the Western world."	2.47	Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. ( Clar, C; Fraser, A; Ghouri, N; Gurung, T; Henderson, R; Preiss, D; Sattar, N; Shyangdan, D; Waugh, N, 2011)
"Insulin resistance is a new target in the challenging management of chronic hepatitis C."	2.46	Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management. ( del Campo, JA; López, RA; Romero-Gómez, M, 2010)
"Insulin resistance is nearly universal in NASH and is thought to play an important role in its pathogenesis leading to dysregulated lipid metabolism."	2.45	Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: Current status. ( Dong, MH; Loomba, R; Stein, LL, 2009)
"Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly."	2.44	[Non-alcoholic fatty liver disease--new view]. ( Lawniczak, M; Marlicz, W; Miezyńska-Kurtycz, J; Milkiewicz, P; Raszeja-Wyszomirska, J, 2008)
"Nonalcoholic steatohepatitis (NASH) is one of the most common liver disorders in North America."	2.44	Treatment of fibrosis in nonalcoholic fatty liver disease. ( Anania, FA; Hoteit, MA, 2007)
"Obesity is not necessary to observe insulin resistance in humans since severe insulin resistance also characterizes patients lacking subcutaneous fat such as those with HAART (highly-active antiretroviral therapy) - associated lipodystrophy."	2.43	The fatty liver and insulin resistance. ( Westerbacka, J; Yki-Järvinen, H, 2005)
"Non-alcoholic steatohepatitis once considered a benign process is now known to lead to progressive fibrosis and cirrhosis."	2.43	Review article: Drug therapy for non-alcoholic fatty liver disease. ( Comar, KM; Sterling, RK, 2006)
"Insulin resistance is an integral part of the underlying pathophysiology in most patients with nonalcoholic fatty liver disease (NAFLD)."	2.43	Therapy of NAFLD: insulin sensitizing agents. ( Al-Osaimi, AM; Argo, CK; Caldwell, SH, 2006)
"Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan."	2.43	[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance]. ( Kawaguchi, K; Korenaga, K; Korenaga, M; Sakaida, I; Uchida, K, 2006)
"Metformin is a widely used drug in the therapy of patients affected by diabetes mellitus."	2.43	Metformin beyond diabetes: new life for an old drug. ( Mannucci, E; Monami, M; Rotella, CM, 2006)
"Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years."	2.42	Metformin: new understandings, new uses. ( Hundal, RS; Inzucchi, SE, 2003)
"Metformin therapy was found to eliminate fatty liver disease in this model."	2.42	Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. ( Barkin, JS; Hookman, P, 2003)
"Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent."	1.91	Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism. ( Chen, H; Huang, H; Liu, Y; Zheng, S, 2023)
"Metformin alone reduced hyperinsulinemia and circulating c-reactive protein, but exacerbated nephropathy."	1.72	Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice. ( Calcutt, NA; Doty, R; Flurkey, K; Harrison, DE; Koza, RA; Reifsnyder, PC, 2022)
"Metformin is increasingly used to treat gestational diabetes (GDM) and pregnancies complicated by pregestational type 2 diabetes or polycystic ovary syndrome but data regarding long-term offspring outcome are lacking in both human studies and animal models."	1.72	Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring. ( Aiken, CE; Ashmore, TJ; Blackmore, HL; Dearden, L; Fernandez-Twinn, DS; Ozanne, SE; Pantaleão, LC; Pellegrini Pisani, L; Schoonejans, JM; Tadross, JA, 2022)
"Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice."	1.43	Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21. ( Byun, JK; Cho, ML; Choi, JY; Jeong, JH; Jhun, JY; Kim, EK; Kim, JK; Lee, SH; Lee, SY, 2016)
"From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included."	1.39	NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients. ( Björnsson, E; Enders, F; Lindor, KD; Suwanwalaikorn, S; Treeprasertsuk, S, 2013)
"Metformin has recently drawn attention because of its potential antitumor effect."	1.39	Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice. ( Aoki, K; Atsumi, T; Inoue, H; Ito, Y; Kaji, M; Nagashima, Y; Nakamura, A; Orime, K; Sakamoto, E; Sato, K; Shirakawa, J; Tajima, K; Terauchi, Y; Togashi, Y, 2013)
"Nonalcoholic fatty liver disease (NAFLD), one of chronic liver diseases, seems to be rising as the obesity epidemic continues."	1.38	Synthesis and biological evaluation of 5-benzylidenepyrimidine-2,4,6(1H,3H,5H)-trione derivatives for the treatment of obesity-related nonalcoholic fatty liver disease. ( Chen, J; Chen, L; Huang, L; Lai, H; Liang, X; Liu, J; Ma, L; Pei, H; Peng, A; Ran, Y; Sang, Y; Wei, Y; Xiang, M; Xie, C, 2012)
"Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance."	1.38	Proteomic analysis of liver mitochondria of apolipoprotein E knockout mice treated with metformin. ( Korbut, R; Madej, J; Okoń, K; Olszanecki, R; Stachowicz, A; Suski, M, 2012)
"Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes."	1.38	Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis. ( Ando, H; Fujimura, A; Hayashi, K; Kaneko, S; Kato, K; Kimura, T; Kita, Y; Kurita, S; Matsuzawa-Nagata, N; Misu, H; Miyamoto, K; Nakanuma, Y; Ni, Y; Ota, T; Otoda, T; Takamura, T; Takeshita, Y; Uno, M; Zen, Y, 2012)
"non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes are associated with dyslipidaemia, inflammation and oxidative stress."	1.37	Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia. ( Amaral, C; Cipriano, A; Crisóstomo, J; Louro, T; Matafome, P; Monteiro, P; Nunes, E; Rodrigues, L; Seiça, R, 2011)
"There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease."	1.31	Metformin reverses fatty liver disease in obese, leptin-deficient mice. ( Chuckaree, C; Diehl, AM; Kuhajda, F; Lin, HZ; Ronnet, G; Yang, SQ, 2000)
"There is no established treatment for steatohepatitis in patients who are not alcoholics."	1.31	Metformin in non-alcoholic steatohepatitis. ( Bianchi, G; Brizi, M; Marchesini, G; Melchionda, N; Tomassetti, S; Zoli, M, 2001)

Research

Studies (166)

Authors

Clinical Trials (32)

Trial Overview

Trial Outcomes

Change in Body Composition

Change in Body Mass Index (BMI)

Change in Total Daily Dose of Insulin (TDI) Per kg

Change in Waist Circumference

Change in Blood Pressure

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Timeframe	Studies, this research(%)	All Research%
pre-1990	4 (2.41)	18.7374
1990's	1 (0.60)	18.2507
2000's	57 (34.34)	29.6817
2010's	95 (57.23)	24.3611
2020's	9 (5.42)	2.80

Authors	Studies
Ma, L	1
Xie, C	1
Ran, Y	1
Liang, X	2
Huang, L	1
Pei, H	1
Chen, J	1
Liu, J	3
Sang, Y	1
Lai, H	1
Peng, A	1
Xiang, M	1
Wei, Y	1
Chen, L	6
Mercado-Gómez, M	1
Prieto-Fernández, E	1
Goikoetxea-Usandizaga, N	1
Vila-Vecilla, L	1
Azkargorta, M	1
Bravo, M	1
Serrano-Maciá, M	1
Egia-Mendikute, L	1
Rodríguez-Agudo, R	1
Lachiondo-Ortega, S	1
Lee, SY	2
Eguileor Giné, A	1
Gil-Pitarch, C	1
González-Recio, I	1
Simón, J	1
Petrov, P	1
Jover, R	1
Martínez-Cruz, LA	1
Ereño-Orbea, J	1
Delgado, TC	1
Elortza, F	1
Jiménez-Barbero, J	1
Nogueiras, R	1
Prevot, V	1
Palazon, A	1
Martínez-Chantar, ML	1
Reifsnyder, PC	1
Flurkey, K	1
Doty, R	1
Calcutt, NA	1
Koza, RA	1
Harrison, DE	1
Schoonejans, JM	1
Blackmore, HL	1
Ashmore, TJ	1
Pantaleão, LC	1
Pellegrini Pisani, L	1
Dearden, L	1
Tadross, JA	1
Aiken, CE	1
Fernandez-Twinn, DS	1
Ozanne, SE	1
Kang, SM	2
Yun, HM	1
Sohn, M	1
Lim, S	2
Zheng, S	1
Huang, H	1
Chen, H	1
Liu, Y	2
Adeshirlarijaney, A	1
Zou, J	1
Tran, HQ	1
Chassaing, B	1
Gewirtz, AT	1
Li, X	2
Wang, L	1
Yang, X	3
Huang, C	1
Liu, Q	2
Li, L	3
Gao, L	1
Li, C	1
Huan, Y	1
Lei, L	1
Cao, H	1
Gao, A	1
Liu, S	1
Shen, Z	1
de Zegher, F	2
Díaz, M	1
Villarroya, J	1
Cairó, M	1
López-Bermejo, A	2
Villarroya, F	1
Ibáñez, L	2
Zhang, X	2
Zhuang, Y	1
Qin, T	1
Chang, M	1
Ji, X	1
Wang, N	1
Zhang, Z	1
Zhou, H	1
Wang, Q	1
Li, JZ	1
Li, M	2
Sharma, A	1
Yin, C	1
Tan, X	1
Xiao, Y	1
Kosi-Trebotic, L	1
Thomas, A	1
Harreiter, J	1
Chmelik, M	1
Trattnig, S	1
Kautzky-Willer, A	1
Glintborg, D	1
Andersen, M	1
Choi, RY	1
Ham, JR	1
Lee, HI	1
Cho, HW	1
Choi, MS	1
Park, SK	1
Lee, J	1
Kim, MJ	1
Seo, KI	1
Lee, MK	1
García Beltrán, C	1
Boudaba, N	1
Marion, A	1
Huet, C	1
Pierre, R	1
Viollet, B	1
Foretz, M	1
Ma, C	1
Zhang, W	1
Liu, L	1
Feng, K	1
Yang, S	1
Sun, L	1
Yu, M	1
Yang, J	1
Hu, W	1
Miao, RQ	1
Zhu, Y	1
Han, J	1
Chen, Y	1
Duan, Y	1
Chang, HH	1
Moro, A	1
Chou, CEN	1
Dawson, DW	1
French, S	1
Schmidt, AI	1
Sinnett-Smith, J	1
Hao, F	1
Hines, OJ	1
Eibl, G	1
Rozengurt, E	1
Zabielski, P	1
Hady, HR	1
Chacinska, M	1
Roszczyc, K	1
Gorski, J	1
Blachnio-Zabielska, AU	1
Belloni, L	1
Di Cocco, S	1
Guerrieri, F	1
Nunn, ADG	1
Piconese, S	1
Salerno, D	1
Testoni, B	1
Pulito, C	1
Mori, F	1
Pallocca, M	1
Sacconi, A	1
Vivoli, E	1
Marra, F	1
Strano, S	1
Blandino, G	1
Levrero, M	1
Pediconi, N	1
Zhang, C	1
Hu, J	1
Sheng, L	1
Yuan, M	1
Wu, Y	1
Zheng, G	1
Qiu, Z	1
Treeprasertsuk, S	1
Björnsson, E	1
Enders, F	1
Suwanwalaikorn, S	1
Lindor, KD	1
Maffioli, P	1
Fogari, E	1
D'Angelo, A	1
Perrone, T	1
Derosa, G	1
Tajima, K	1
Nakamura, A	1
Shirakawa, J	1
Togashi, Y	1
Orime, K	1
Sato, K	1
Inoue, H	1
Kaji, M	1
Sakamoto, E	1
Ito, Y	1
Aoki, K	1
Nagashima, Y	1
Atsumi, T	1
Terauchi, Y	1
Younossi, ZM	1
Reyes, MJ	1
Mishra, A	1
Mehta, R	1
Henry, L	1
Liu, F	1
Wang, C	2
Zhang, L	1
Xu, Y	3
Jang, L	1
Gu, Y	1
Cao, X	1
Zhao, X	1
Ye, J	1
Li, Q	2
Fruci, B	3
Giuliano, S	2
Mazza, A	3
Malaguarnera, R	2
Belfiore, A	3
Mazzella, N	1
Ricciardi, LM	1
Mazzotti, A	1
Marchesini, G	7
Linden, MA	1
Fletcher, JA	1
Morris, EM	1
Meers, GM	1
Kearney, ML	1
Crissey, JM	1
Laughlin, MH	1
Booth, FW	1
Sowers, JR	1
Ibdah, JA	1
Thyfault, JP	1
Rector, RS	1
Fan, H	1
Pan, Q	1
Hong, ES	1
Kim, EK	2
Khang, AR	1
Choi, SH	1
Park, KS	1
Jang, HC	1
Woo, SL	1
Xu, H	1
Li, H	1
Zhao, Y	1
Hu, X	1
Zhao, J	1
Guo, X	1
Guo, T	1
Botchlett, R	1
Qi, T	1
Pei, Y	1
Zheng, J	1
An, X	1
Xiao, X	1
Huo, Y	1
Wu, C	1
Shu, Y	1
Chen, EC	1
Yee, SW	2
Zur, AA	1
Li, S	1
Xu, L	1
Keshari, KR	1
Lin, MJ	1
Chien, HC	1
Zhang, Y	2
Morrissey, KM	1
Ostrem, J	1
Younger, NS	1
Kurhanewicz, J	1
Shokat, KM	1
Ashrafi, K	1
Giacomini, KM	2
Yang, L	1
Song, MQ	1
Zhang, QL	1
Shou, L	1
Zang, SF	1
Yang, YL	1
Pala, L	1
Barbaro, V	1
Dicembrini, I	1
Rotella, CM	2
Song, YM	2
Lee, YH	2
Kim, JW	1
Ham, DS	1
Kang, ES	2
Cha, BS	2
Lee, HC	1
Lee, BW	2
Macauley, M	1
Hollingsworth, KG	2
Smith, FE	1
Thelwall, PE	1
Al-Mrabeh, A	1
Schweizer, A	1
Foley, JE	1
Taylor, R	2
Tang, A	1
Rabasa-Lhoret, R	1
Castel, H	1
Wartelle-Bladou, C	1
Gilbert, G	1
Massicotte-Tisluck, K	1
Chartrand, G	1
Olivié, D	1
Julien, AS	1
de Guise, J	1
Soulez, G	1
Chiasson, JL	1
Cassidy, S	1
Thoma, C	1
Hallsworth, K	1
Parikh, J	1
Jakovljevic, DG	1
Trenell, MI	1
Wang, FZ	1
Xie, ZS	1
Xing, L	1
Zhang, BF	1
Zhang, JL	1
Cui, PF	1
Qiao, JB	1
Shi, K	1
Cho, CS	1
Cho, MH	1
Xu, X	1
Li, P	1
Jiang, HL	1
Kutbay, NO	1
Yurekli, BS	1
Onay, H	1
Altay, CT	1
Atik, T	1
Hekimsoy, Z	1
Saygili, F	1
Akinci, B	1
Lee, WK	1
García-Heredia, A	1
Riera-Borrull, M	1
Fort-Gallifa, I	1
Luciano-Mateo, F	1
Cabré, N	1
Hernández-Aguilera, A	1
Joven, J	1
Camps, J	1
Meng, X	1
Guo, J	1
Fang, W	1
Dou, L	1
Huang, X	1
Zhou, S	1
Man, Y	1
Tang, W	1
Yu, L	1
Li, J	2
Lee, SH	1
Jhun, JY	1
Byun, JK	1
Jeong, JH	1
Kim, JK	1
Choi, JY	1
Cho, ML	1
Tang, X	1
Xiang, W	1
Cui, Y	1
Xie, B	1
Wang, X	1
Xu, Z	1
Gan, L	1
Lu, CH	1
Hung, YJ	1
Hsieh, PS	1
Mubeen, S	1
Amjad, Z	1
Memon, FM	1
Ashraf, SU	1
Takemori, H	1
Fu, J	1
Xu, M	1
Xiong, L	1
Li, N	2
Wen, X	1
Nobili, V	3
Manco, M	1
Ciampalini, P	1
Alisi, A	2
Devito, R	1
Bugianesi, E	3
Marcellini, M	1
Raszeja-Wyszomirska, J	1
Lawniczak, M	1
Marlicz, W	1
Miezyńska-Kurtycz, J	1
Milkiewicz, P	1
Nadeau, KJ	1
Ehlers, LB	1
Zeitler, PS	1
Love-Osborne, K	1
Nar, A	1
Gedik, O	1
Loomba, R	2
Lutchman, G	1
Kleiner, DE	2
Ricks, M	1
Feld, JJ	1
Borg, BB	1
Modi, A	1
Nagabhyru, P	1
Sumner, AE	1
Liang, TJ	1
Hoofnagle, JH	2
Kashi, MR	1
Torres, DM	2
Harrison, SA	2
Patton, HM	1
Lavine, JE	8
Van Natta, ML	2
Schwimmer, JB	6
Kleiner, D	1
Molleston, J	1
Vuppalanchi, R	1
Chalasani, N	5
Raso, GM	1
Esposito, E	1
Iacono, A	1
Pacilio, M	1
Cuzzocrea, S	1
Canani, RB	1
Calignano, A	1
Meli, R	1
Fischer, R	1
Shneider, B	1
Mascitelli, L	1
Pezzetta, F	1
Goldstein, MR	1
Socha, P	2
Horvath, A	1
Vajro, P	1
Dziechciarz, P	1
Dhawan, A	1
Szajewska, H	1
Forcheron, F	1
Abdallah, P	1
Basset, A	1
del Carmine, P	1
Haffar, G	1
Beylot, M	1
Omer, Z	1
Cetinkalp, S	1
Akyildiz, M	1
Yilmaz, F	1
Batur, Y	1
Yilmaz, C	1
Akarca, U	1
Molleston, JP	2
Scheimann, AO	2
Murray, KF	2
Abrams, SH	2
Rosenthal, P	2
Sanyal, AJ	3
Robuck, PR	2
Brunt, EM	3
Unalp, A	2
Tonascia, J	2
Haukeland, JW	2
Konopski, Z	2
Eggesbø, HB	1
von Volkmann, HL	1
Raschpichler, G	1
Bjøro, K	1
Haaland, T	2
Løberg, EM	2
Birkeland, K	1
Stein, LL	1
Dong, MH	1
Jin, X	1
Yu, CH	1
Chen, SH	1
Li, WP	1
Li, YM	1
Garinis, GA	2
De Siena, M	1
Abenavoli, S	1
Gulletta, E	1
Ventura, V	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Omics-based Predictors of NAFLD/Potential NASH: A New Era Towards Valid and Reliable Non-invasive Diagnosis and Personalized Therapy[NCT05301231]		450 participants (Anticipated)	Observational [Patient Registry]	2022-08-01	Not yet recruiting
A Single-center,Double-blind,Randomised,Placebo-controlled,Parallel-group Study to Assess the Effect of 24 Weeks of Treatment With Vildagliptin on Insulin Sensitivity and Its Underlying Mechanism in Patients With T2DM Treated With Metformin[NCT01356381]	Phase 4	43 participants (Actual)	Interventional	2011-04-30	Completed
Randomized Trial of Liraglutide and Insulin Therapy on Hepatic Steatosis as Measured by MRI and MRS in Metformin-treated Patients With Type 2 Diabetes: an Open Pilot Study[NCT01399645]	Phase 2	35 participants (Actual)	Interventional	2011-05-31	Completed
Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (T1D)--Insulin Clamp Ancillary Study for Assessment of Insulin Resistance[NCT02045290]	Phase 3	37 participants (Actual)	Interventional	2014-01-31	Completed
A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes[NCT01881828]	Phase 3	164 participants (Actual)	Interventional	2013-09-30	Completed
Improving Insulin Resistance to Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study[NCT02457286]	Phase 1	0 participants (Actual)	Interventional	2015-06-30	Withdrawn (stopped due to patients do not want to participate)
A Pilot Study: Metformin as an Inflammatory Modulating Therapy in Older Adults Without Diabetes[NCT03772964]	Phase 1/Phase 2	32 participants (Actual)	Interventional	2019-01-22	Completed
Treatment of Nonalcoholic Steatohepatitis With Metformin[NCT00063232]	Phase 2	28 participants (Actual)	Interventional	2003-06-30	Completed
Prevalence of NAFLD and Correlation With Its Main Risk Factors Among Egyptian Multicenter National Study[NCT04081571]		1,080 participants (Anticipated)	Observational	2019-04-01	Recruiting
Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)[NCT00063635]	Phase 3	173 participants (Actual)	Interventional	2005-09-30	Completed
Double Blind, Randomized, Placebo Controlled Trial With Metformin in Non-Alcoholic Fatty Liver Disease (NAFLD)[NCT00303537]	Phase 2/Phase 3	90 participants (Anticipated)	Interventional	2004-11-30	Active, not recruiting
[NCT01084486]	Phase 1/Phase 2	0 participants	Interventional		Completed
Effect of Exenatide Treatment on Hepatic Fat Content and Plasma Adipocytokine Levels in Patients With Type 2 Diabetes Mellitus[NCT01432405]	Phase 4	24 participants (Actual)	Interventional	2007-06-30	Completed
Pilot Randomized Controlled Trial of Spironolactone in Young Women With Nonalcoholic Steatohepatitis (NASH)[NCT03576755]	Phase 1/Phase 2	20 participants (Actual)	Interventional	2019-01-09	Completed
Influence of Hepatic Inflammation and Hepatocellular Apoptosis on Physical Performance and Training Effect in Patients With Non - Alcoholic Steatohepatitis[NCT02526732]		44 participants (Actual)	Interventional	2015-09-30	Completed
The Effects of Type of Exercise on Hepatic Fat Content and Metabolic Profiles in Non-alcoholic Fatty Liver Disease: A Randomized Trial[NCT02679417]		38 participants (Actual)	Interventional	2015-08-31	Completed
A Single Center, Non-randomized Study to Evaluate the Safety and Efficacy of Left Gastric Artery Embolization, to Promote Short-term Weight Loss in Obese Patients With Nonalcoholic Steatohepatitis (NASH) and Thereby Improve NASH[NCT02933554]		8 participants (Anticipated)	Interventional	2024-06-30	Not yet recruiting
Non-invasive Evaluation of Liver Fibrosis, Steatosis, and Nonalcoholic Steatohepatitis in Biopsy-Proven NAFLD Patients[NCT03725631]		150 participants (Anticipated)	Interventional	2016-09-01	Recruiting
Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial[NCT03198572]	Phase 4	120 participants (Anticipated)	Interventional	2017-08-16	Recruiting
Comparative Clinical Study to Evaluate the Possible Beneficial Effect of Empagliflozin Versus Pioglitazone on Non-diabetic Patients With Non-Alcoholic Steatohepatitis[NCT05605158]	Phase 3	56 participants (Anticipated)	Interventional	2022-11-30	Not yet recruiting
An Open-Label Pilot Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Potential of Oral Insulin to Reduce Liver Fat Content and Fibrosis in Patients With Nonalcolholic Steatohepatitis (NASH)[NCT02653300]	Phase 2	10 participants (Actual)	Interventional	2018-09-20	Completed
Assessment of Chronic Kidney Disease in Non Alcoholic Fatty Liver Disease(NAFLD) Patients[NCT04779905]		62 participants (Actual)	Observational	2021-02-28	Completed
Development of Non-invasive Magnetic Resonance Imaging Diagnostic Method for Nonalcoholic Steatohepatitis(NASH)[NCT03375008]		47 participants (Actual)	Interventional	2016-09-08	Completed
A Phase 2, Prospective, Multicenter, Double-blind, Randomized Study of Saroglitazar Magnesium 1 mg, 2 mg or 4 mg Versus Placebo in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis[NCT03061721]	Phase 2	106 participants (Actual)	Interventional	2017-04-06	Completed
A Double-Blind, Randomized, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Oral Insulin to Reduce Liver Fat Content in Type 2 Diabetes Patients With Nonalcoholic Steatohepatitis (NASH)[NCT04618744]	Phase 2	33 participants (Actual)	Interventional	2020-11-24	Completed
Combined Nutritional and Exercise Strategies to Reduce Liver Fat Content in Patients With Type 2 Diabetes[NCT01025856]		45 participants (Actual)	Interventional	2009-09-30	Completed
Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population[NCT05317806]	Phase 4	15 participants (Anticipated)	Interventional	2022-10-10	Active, not recruiting
Double-blind, Randomized Clinical Trial to Evaluate Effect of Combination Therapy of Metformin and Sibutramine Versus Metformin or Sibutramine Monotherapy Over Weight, Adiposity, Glucose Metabolism and Inflammatory State in Obese Patients[NCT00941382]	Phase 3	60 participants (Anticipated)	Interventional	2008-11-30	Active, not recruiting
Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly[NCT04841668]		136 participants (Anticipated)	Observational	2021-04-10	Recruiting
A Randomized, Placebo-controlled, Double-blind Multicenter Phase II Study to Investigate the Protectivity and Efficacy of Metformin Against Steatosis in Combination With FOLFIRI and Cetuximab in Subjects With First-line Palliative Treated, KRAS-Wild-Type,[NCT01523639]	Phase 2	8 participants (Actual)	Interventional	2012-04-30	Terminated (stopped due to Prematurely due to slow recruitment (07/08/2013). Newly defined study end=LPLV=05/11/2013. ABCSG guaranteed completed treatment period for ethical reasons.)
Lifestyle Intervention and Antioxidants in Children With Nonalcoholic Fatty Liver Disease: A Randomized, Controlled Trial[NCT00655018]	Phase 2/Phase 3	90 participants (Actual)	Interventional	2003-01-31	Completed
Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH)[NCT00845845]	Phase 2	12 participants (Actual)	Interventional	2006-03-31	Terminated (stopped due to Terminated due to low enrollment.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	percentage of change (Mean)
Metformin	-0
Oral Placebo	1

Intervention	percentile (Mean)
Metformin	-1
Oral Placebo	1

Intervention	insulin per kg (Mean)
Metformin	-0.1
Oral Placebo	-0.0

Intervention	centimeters (Mean)
Metformin	-0
Oral Placebo	1

Intervention	mm Hg (Mean)
	Change in Systolic	Change in Diastolic
Metformin	0	0
Oral Placebo	-0	0

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Intervention	percentage (Mean)
	HbA1c	Change from Baseline to 26 Weeks
Metformin	9.0	0.2
Oral Placebo	8.9	0.2

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

Change in Serum Lipids

Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.

Intervention	percentage of participants (Number)
	HbA1c Decrease ≥0.5%	HbA1c Increase ≥0.5%	HbA1c <7.5%
Metformin	19	44	3
Oral Placebo	18	35	4

Intervention	mg/dL (Mean)
	Change in LDL	Change in VLDL	Change in HDL	Change in Triglycerides	Change in Total Cholesterol
Metformin	-6	-0	-0	4	-5
Oral Placebo	2	1	-1	6	3

Grip strength over time. (NCT03772964)
Timeframe: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)

Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.

Intervention	mmHg (Mean)
	0 days	90 days, compared to 0 days	120 days, compared to 0 days
1000mg Exposure	28.9	-0.4	1.1
1500mg Exposure	25.7	-.2	.3
500mg Exposure	28.2	-5.3	.1
Placebo	25.7	-.3	-.6

The SPPB is a group of measures that combines the results of the gait speed, chair stand and balance tests. The minimum is zero (worse performance) and the maximum is 12 (best performance). (NCT03772964)
Timeframe: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)

Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.

Intervention	Units on a scale (Mean)
	0d	90d, change from 0d	120d, change from 0d
1000mg Exposure	10.8	0.4	0.2
1500mg Exposure	11.1	0.4	0.3
500mg Exposure	11.2	-0.3	0
Placebo	10.6	1.0	0.5

Aggregometry area under the curve with the Y-axis being % aggregometry and the X-axis time in minutes. (NCT03772964)
Timeframe: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)

Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.

Intervention	arbitrary units*mins (Mean)
	0 days	30 day change from day 0	60 days change from day 0	90 days change from day 0	120 days change from day 0
1000mg Exposure	67	8.9	-23.5	2.4	1.0
1500mg Exposure	196	-166.7	-139.8	-222.5	-196.7
500mg Exposure	56.3	-34.7	-28.3	1.6	-49.2
Placebo	83.3	-29.6	-49.4	-66.6	-47.6

"Bacterial communities using 16S rRNA sequencing in relationship to metformin dosing over time. Species richness or diversity in the sample is measured by Choa1 metric. Chao1 is an estimate of how many species are present in an ecosystem. In general, having more species is considered to be healthier and these values typically range from 100-200 for fecal samples. The Chao1 index over numerous samples across time are explored to understand treatment effects." (NCT03772964)
Timeframe: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)

Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline

Intervention	Index (Mean)
	Day 0	Day 30	Day 60	Day 90	Day 120
1000mg Exposure	107.6	130.7	137.9	135	142.2
1500mg Exposure	128.1	128.1	128.6	138.2	144.2
500mg Exposure	136.5	139.9	121.4	137.8	134
Placebo	141.5	144.75	134.3	152	159.2

HOMA-IR is calculated from Fasting Glucose and Fasting Insulin (NCT00063232)
Timeframe: from baseline to 48 weeks

Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)

Intervention	unit (Mean)
Metformin	-3.3

Alanine transaminase <42 U/L is considered normal (NCT00063232)
Timeframe: from baseline to 48 weeks

Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)

Intervention	participants (Number)
	changed to normal from abnormal	unchanged (normal at beginning)	unchanged (abnormal at beginning)	changed to abnormal from normal
Metformin	9	4	12	1

Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies. (NCT00063232)
Timeframe: from baseline to 48 Weeks

Change in Body Mass Index

Change in Nonalcoholic Fatty Liver Disease (NAFLD) Score (Histologic Feature Scores Determined by Standardized Scoring of Liver Biopsies) From Baseline at 96 Weeks of Treatment

Intervention	participants (Number)
	improved (reduced) by greater or equal to 3 points	improved (reduced) by 1-2 points	no change	worsen (increased)
Metformin	9	11	5	1

Intervention	kg/m-squared (Mean)
Metformin	1.3
Vitamin E	2.1
Placebo	1.9

Histological activity was assessed using the NAFLD activity score on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (0-3), lobular inflammation (0-3), and hepatocellular ballooning (0-2). (NCT00063635)
Timeframe: baseline and 96 weeks

Change in QOL- Psychosocial Health

Intervention	units on a scale (Mean)
Metformin	-1.1
Vitamin E	-1.8
Placebo	-0.7

Change in self-reported QOL physical health Pediatric Quality of Life Inventory (version 4.0) scores were recorded to range from 0 to 100 with increasing scores indicating better quality of life. (NCT00063635)
Timeframe: baseline and 96 weeks

Change in Quality of Life (QOL) Scores- Physical Health

Intervention	units on a scale (Mean)
Metformin	4.0
Vitamin E	6.0
Placebo	5.6

Change in Serum Aspartate Aminotransferase (AST)

Change in Serum Vitamin E Levels

Number of Participants With Improvement in Ballooning Degradation Score

Intervention	units on a scale (Mean)
Metformin	5.4
Vitamin E	7.6
Placebo	5.4

Intervention	IU/L (Mean)
Metformin	-21.5
Vitamin E	-22.8
Placebo	-20.4

Intervention	mg/L (Mean)
Metformin	-0.5
Vitamin E	9.4
Placebo	-0.9

Ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe ballooning. This secondary outcome measure is the number of participants that experienced a decrease in ballooning score at 96 weeks compared to baseline, which indicates improvement in ballooning. (NCT00063635)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Liver Fibrosis Score

Intervention	participants (Number)
Metformin	22
Vitamin E	22
Placebo	10

Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score at 96 weeks compared to baseline, which indicates improvement in fibrosis. (NCT00063635)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Lobular Inflammation Score

Intervention	participants (Number)
Metformin	22
Vitamin E	18
Placebo	19

Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score at 96 weeks compared to baseline, which indicates improvement in lobular inflammation. (NCT00063635)
Timeframe: baseline and 96 weeks

Number of Participants With Improvement in Steatosis Score

Intervention	participants (Number)
Metformin	23
Vitamin E	22
Placebo	20

Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score at 96 weeks compared to baseline, which indicates improvement in steatosis. (NCT00063635)
Timeframe: baseline and 96 weeks

Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L

Intervention	participants (Number)
Metformin	26
Vitamin E	27
Placebo	19

The primary outcome was sustained reduction in ALT level, defined as 50% or less of the baseline level or 40 IU/L or less at each visit from 48 to 96 weeks of treatment. (NCT00063635)
Timeframe: baseline and 96 weeks

Hepatic Fat

Intervention	participants (Number)
Metformin	9
Vitamin E	15
Placebo	10

The effect of exenatide and pioglitazone on liver fat content after one year of treatment in patients with type 2 diabetes. (NCT01432405)
Timeframe: one year

Plasma Adipocytokines

Intervention	percent of liver fat (Mean)
Pioglitazone and Exenatide	4.7
Pioglitazone	6.5

the effect of the intervention on plasma adiponectin levels. (NCT01432405)
Timeframe: one year

Change in MRI-Proton Density Fat Fraction (MRI-PDFF)

Intervention	microgram per ml (Mean)
Pioglitazone and Exenatide	23.2
Pioglitazone	15.8

Absolute Change in MRI-Proton Density Fat Fraction (expressed as percent fat in the liver) from baseline to week 12 (NCT02653300)
Timeframe: Two timepoints: Baseline (week 0) and Week 12

Mean Fibrosis Score CAP™ (FibroMax)

Intervention	percentage fat in the liver (Mean)
	MRPDFF (%) at baseline	MR PDFF (%) at Week 12	Absolute Mean Change in MR PDFF (%) from Baseline
Oral Insulin	21.3	14.4	-6.9

Mean fibrosis score (severity scale of liver fibrosis) measured at baseline and week 12. Fibrosis Score CAP measures the amount of steatosis (fatty change) in the liver. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m with higher values indicating more fatty change (NCT02653300)
Timeframe: Two timepoints: Baseline (week 0) and Week 12

Mean Transient Elastography Measurement (Fibroscan)

Intervention	dB/M (Mean)
	Mean Fibrosis Score at Baseline	Mean Fibrosis Score at week 12
Oral Insulin	338.5	315.5

Mean Transient elasticity, measured in kPA (kilo Pascal), (NCT02653300)
Timeframe: Two timepoints: Baseline (week 0) and Week 12

Article	Year
Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review. Current opinion in obstetrics & gynecology, 2017, Volume: 29, Issue:6 Topics: Body Mass Index; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Fatty Liver; Femal	2017
Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets. Alimentary pharmacology & therapeutics, 2014, Volume: 39, Issue:1 Topics: Bariatric Surgery; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Me	2014
Nonalcoholic Fatty liver: a possible new target for type 2 diabetes prevention and treatment. International journal of molecular sciences, 2013, Nov-20, Volume: 14, Issue:11 Topics: Diabetes Mellitus, Type 2; Disease Progression; Fatty Liver; Humans; Hypoglycemic Agents; Insulin Re	2013
The role of medications for the management of patients with NAFLD. Clinics in liver disease, 2014, Volume: 18, Issue:1 Topics: Antioxidants; Fatty Liver; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Me	2014
The therapy of insulin resistance in other diseases besides type 2 diabetes. Eating and weight disorders : EWD, 2014, Volume: 19, Issue:3 Topics: Fatty Liver; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Obesity; Polycystic	2014
[Non-alcoholic fatty liver disease--new view]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2008, Volume: 24, Issue:144 Topics: Biopsy; Causality; Comorbidity; Disease Progression; Fatty Liver; Humans; Hyperglycemia; Insulin Res	2008
Current and emerging therapies in nonalcoholic fatty liver disease. Seminars in liver disease, 2008, Volume: 28, Issue:4 Topics: Animals; Antioxidants; Bariatric Surgery; Body Mass Index; Cannabinoids; Cholagogues and Choleretics	2008
Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology (Baltimore, Md.), 2009, Volume: 49, Issue:1 Topics: Bariatric Surgery; Biomarkers; Biopsy; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type	2009
Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review. Journal of pediatric gastroenterology and nutrition, 2009, Volume: 48, Issue:5 Topics: Acetylcysteine; Adult; Alanine Transaminase; Aspartate Aminotransferases; Carnitine; Child; Dietary	2009
Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: Current status. Advances in therapy, 2009, Volume: 26, Issue:10 Topics: Fatty Liver; Glucagon-Like Peptide 1; Glucose; Humans; Hypoglycemic Agents; Insulin Resistance; Metf	2009
Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management. Digestive diseases (Basel, Switzerland), 2010, Volume: 28, Issue:1 Topics: Animals; Antiviral Agents; Diabetes Mellitus, Type 2; Fatty Liver; Glucose Clamp Technique; Hepatiti	2010
Novel drugs in familial combined hyperlipidemia: lessons from type 2 diabetes mellitus. Current opinion in lipidology, 2010, Volume: 21, Issue:6 Topics: Adipose Tissue; Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Discovery; Fatty Liver; Genetic Pr	2010
Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2010, Volume: 32, Issue:10 Topics: Fatty Liver; Humans; Hypoglycemic Agents; Insulin; Metformin; Randomized Controlled Trials as Topic;	2010
Therapeutic trials in nonalcoholic steatohepatitis: insulin sensitizers and related methodological issues. Hepatology (Baltimore, Md.), 2010, Volume: 52, Issue:6 Topics: Clinical Trials as Topic; Fatty Liver; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Met	2010
[Fatty liver and its clinical management in obese adolescents]. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion, 2011, Volume: 58, Issue:1 Topics: Adiponectin; Adolescent; Apoptosis; Biomarkers; Chemokines; Disease Progression; Fatty Liver; Fibros	2011
Use of metformin in pediatric age. Pediatric diabetes, 2011, Volume: 12, Issue:6 Topics: Adolescent; Antipsychotic Agents; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fatty	2011
Nonalcoholic fatty liver disease and type 2 diabetes mellitus: the hidden epidemic. The American journal of the medical sciences, 2011, Volume: 341, Issue:6 Topics: Bariatric Surgery; Biopsy; Diabetes Mellitus, Type 2; Disease Progression; Exercise; Fatty Liver; Hu	2011
Management of metabolic syndrome in children and adolescents. Nutrition, metabolism, and cardiovascular diseases : NMCD, 2011, Volume: 21, Issue:6 Topics: Adolescent; Antioxidants; Cardiovascular Diseases; Child; Cholesterol, HDL; Cholesterol, LDL; Diabet	2011
Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. Health technology assessment (Winchester, England), 2011, Volume: 15, Issue:38 Topics: Biopsy; Databases, Bibliographic; Diagnosis, Differential; Fatty Liver; Humans; Hypoglycemic Agents;	2011
The role of metformin in the management of NAFLD. Experimental diabetes research, 2012, Volume: 2012 Topics: Fatty Liver; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin	2012
Neuroendocrine and endocrine dysfunction in the hyperinsulinemic PCOS patient: the role of metformin. Minerva endocrinologica, 2012, Volume: 37, Issue:1 Topics: Adipokines; Androgens; Endocrine System; Fatty Acids, Nonesterified; Fatty Liver; Female; Hormones;	2012
Mechanisms involved in the protective effects of metformin against nonalcoholic fatty liver disease. Current medicinal chemistry, 2012, Volume: 19, Issue:18 Topics: Animals; Fatty Liver; Humans; Hypoglycemic Agents; Liver; Metformin; Non-alcoholic Fatty Liver Disea	2012
Pharmacologic therapy for nonalcoholic fatty liver disease in adults. Pharmacotherapy, 2013, Volume: 33, Issue:2 Topics: Adult; Animals; Disease Progression; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibi	2013
Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD. Current pharmaceutical design, 2013, Volume: 19, Issue:29 Topics: Carcinoma, Hepatocellular; Child; Fatty Liver; Humans; Hypoglycemic Agents; Liver Neoplasms; Metform	2013
Metformin: new understandings, new uses. Drugs, 2003, Volume: 63, Issue:18 Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Fatty Liver; Female; HIV I	2003
Metformin: new understandings, new uses. Drugs, 2003, Volume: 63, Issue:18 Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Fatty Liver; Female; HIV I	2003
Metformin: new understandings, new uses. Drugs, 2003, Volume: 63, Issue:18 Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Fatty Liver; Female; HIV I	2003
Metformin: new understandings, new uses. Drugs, 2003, Volume: 63, Issue:18 Topics: Anti-Obesity Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Fatty Liver; Female; HIV I	2003
Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. The American journal of gastroenterology, 2003, Volume: 98, Issue:9 Topics: Adult; Animals; Biochemical Phenomena; Biochemistry; Biopsy, Needle; Clinical Trials as Topic; Disea	2003
Nonalcoholic fatty liver disease in the pediatric population. Clinics in liver disease, 2004, Volume: 8, Issue:3 Topics: Adolescent; Alanine Transaminase; Child; Fatty Liver; Female; Histocytochemistry; Humans; Hypoglycem	2004
Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): treatment. Best practice & research. Clinical gastroenterology, 2004, Volume: 18, Issue:6 Topics: Antioxidants; Cholagogues and Choleretics; Cytoprotection; Enzyme Inhibitors; Fatty Liver; Humans; H	2004
The fatty liver and insulin resistance. Current molecular medicine, 2005, Volume: 5, Issue:3 Topics: Adiponectin; Adipose Tissue; Alanine Transaminase; Animals; Antiretroviral Therapy, Highly Active; C	2005
[Medical management of primary nonalcoholic fatty liver disease]. Medicina clinica, 2005, Jun-18, Volume: 125, Issue:3 Topics: Anti-Obesity Agents; Anticholesteremic Agents; Atorvastatin; Chromans; Diabetes Mellitus, Type 2; Fa	2005
Review article: the treatment of fatty liver disease associated with the metabolic syndrome. Alimentary pharmacology & therapeutics, 2005, Volume: 22 Suppl 2 Topics: Adult; Fatty Liver; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Metabolic Syndrome;	2005
[Therapeutic options for nonalcoholic fatty liver disease and steatohepatitis]. Der Internist, 2005, Volume: 46, Issue:12 Topics: Diet Therapy; Exercise Therapy; Fatty Liver; Fatty Liver, Alcoholic; Humans; Liver Cirrhosis; Liver	2005
Review article: Drug therapy for non-alcoholic fatty liver disease. Alimentary pharmacology & therapeutics, 2006, Jan-15, Volume: 23, Issue:2 Topics: Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Ascorbic Acid; Betaine; Cholagogues and Chol	2006
Therapy of NAFLD: insulin sensitizing agents. Journal of clinical gastroenterology, 2006, Volume: 40 Suppl 1 Topics: Fatty Liver; Humans; Hypoglycemic Agents; Insulin Resistance; Metformin; Thiazolidinediones	2006
Treatment of nonalcoholic fatty liver disease. World journal of gastroenterology, 2006, Apr-14, Volume: 12, Issue:14 Topics: Alanine Transaminase; Animals; Antioxidants; Body Mass Index; Fatty Liver; Humans; Hypolipidemic Age	2006
[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance]. Nihon rinsho. Japanese journal of clinical medicine, 2006, Volume: 64, Issue:6 Topics: Fatty Liver; Humans; Hypoglycemic Agents; Insulin Resistance; Metabolic Syndrome; Metformin; Pioglit	2006
Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review. World journal of gastroenterology, 2006, Dec-28, Volume: 12, Issue:48 Topics: Controlled Clinical Trials as Topic; Diet, Carbohydrate-Restricted; Fatty Liver; Humans; Hypoglycemi	2006
Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. The Cochrane database of systematic reviews, 2007, Jan-24, Issue:1 Topics: Alanine Transaminase; Aspartate Aminotransferases; Fatty Liver; Humans; Hypoglycemic Agents; Insulin	2007
Treatment of fibrosis in nonalcoholic fatty liver disease. Current gastroenterology reports, 2007, Volume: 9, Issue:1 Topics: Adiponectin; Adipose Tissue; Animals; Antioxidants; Cytokines; Fatty Liver; Humans; Hypoglycemic Age	2007
[Pathogenetic treatment of non-alcoholic steatohepatitis: arguments, efficacy, safety]. Terapevticheskii arkhiv, 2007, Volume: 79, Issue:8 Topics: Exercise Therapy; Fatty Acids; Fatty Liver; Humans; Hypoglycemic Agents; Immunologic Factors; Metfor	2007
Use of insulin sensitizers in NASH. Endocrinology and metabolism clinics of North America, 2007, Volume: 36, Issue:4 Topics: Alanine Transaminase; Chromans; Fatty Liver; Humans; Insulin Resistance; Metabolic Syndrome; Metform	2007
Metformin beyond diabetes: new life for an old drug. Current diabetes reviews, 2006, Volume: 2, Issue:3 Topics: Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus, Type 2; Fatty Liver; Female; Humans; Hypoglyc	2006

Article	Year
Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study. Diabetes, obesity & metabolism, 2023, Volume: 25, Issue:7 Topics: Blood Glucose; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV In	2023
The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat. Scientific reports, 2021, 03-29, Volume: 11, Issue:1 Topics: Adolescent; Adult; Case-Control Studies; Child; Fatty Liver; Female; Growth Differentiation Factor 1	2021
Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation. Hormone research in paediatrics, 2018, Volume: 89, Issue:2 Topics: Adiposity; Fatty Liver; Female; Humans; Hypoglycemic Agents; Intra-Abdominal Fat; Life Style; Metfor	2018
Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin. European journal of gastroenterology & hepatology, 2013, Volume: 25, Issue:9 Topics: Adipokines; Aged; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2	2013
Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. Arquivos brasileiros de endocrinologia e metabologia, 2013, Volume: 57, Issue:9 Topics: Adiponectin; Adult; Aged; Alanine Transaminase; Blood Glucose; Body Mass Index; Body Weight; C-React	2013
Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study. Journal of gastroenterology and hepatology, 2014, Volume: 29, Issue:7 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Blood Glucose; Carnitine; DNA	2014
Effect of piglitazone and metformin on retinol-binding protein-4 and adiponectin in patients with type 2 diabetes mellitus complicated with non-alcohol fatty acid liver diseases. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 2014, Volume: 36, Issue:3 Topics: Adiponectin; Adult; Aged; Diabetes Mellitus, Type 2; Fatty Liver; Female; Humans; Male; Metformin; M	2014
Effect of vildagliptin on hepatic steatosis. The Journal of clinical endocrinology and metabolism, 2015, Volume: 100, Issue:4 Topics: Adamantane; Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration	2015
Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. Diabetes care, 2015, Volume: 38, Issue:7 Topics: Adipose Tissue; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Liv	2015
High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial. Diabetologia, 2016, Volume: 59, Issue:1 Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diastole; Diet; Exercise; E	2016
Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Clinical therapeutics, 2008, Volume: 30, Issue:6 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Biopsy; Body Mass Index; Child; Fatty	2008
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatric diabetes, 2009, Volume: 10, Issue:1 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;	2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatric diabetes, 2009, Volume: 10, Issue:1 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;	2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatric diabetes, 2009, Volume: 10, Issue:1 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;	2009
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatric diabetes, 2009, Volume: 10, Issue:1 Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Body Mass Index; Body Weight; Child;	2009
The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta diabetologica, 2009, Volume: 46, Issue:2 Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 2; Exercise; Fatty Liver; Female; Glycated Hemoglobi	2009
Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2009, Volume: 29, Issue:2 Topics: Adult; Biopsy; Fatty Liver; Female; Humans; Hypoglycemic Agents; Liver; Male; Metformin; Middle Aged	2009
Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2009, Volume: 29, Issue:2 Topics: Adult; Biopsy; Fatty Liver; Female; Humans; Hypoglycemic Agents; Liver; Male; Metformin; Middle Aged	2009
Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2009, Volume: 29, Issue:2 Topics: Adult; Biopsy; Fatty Liver; Female; Humans; Hypoglycemic Agents; Liver; Male; Metformin; Middle Aged	2009
Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2009, Volume: 29, Issue:2 Topics: Adult; Biopsy; Fatty Liver; Female; Humans; Hypoglycemic Agents; Liver; Male; Metformin; Middle Aged	2009
Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology, 2008, Volume: 135, Issue:6 Topics: Adolescent; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biopsy; Child; Drug The	2008
Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease. European journal of gastroenterology & hepatology, 2010, Volume: 22, Issue:1 Topics: Adult; Biopsy; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Liver; Fem	2010
Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemporary clinical trials, 2010, Volume: 31, Issue:1 Topics: Adolescent; Alanine Transaminase; Child; Double-Blind Method; Fatty Liver; Female; Humans; Hypoglyce	2010
Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scandinavian journal of gastroenterology, 2009, Volume: 44, Issue:7 Topics: Administration, Oral; Adult; Biopsy; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Fatty L	2009
Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study. International journal of obesity (2005), 2010, Volume: 34, Issue:8 Topics: Adult; Body Mass Index; Diet; Fatty Liver; Female; Humans; Hypoglycemic Agents; Male; Metformin; Non	2010
Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity (Silver Spring, Md.), 2010, Volume: 18, Issue:9 Topics: Adult; Alanine Transaminase; Biomarkers; Diabetes Mellitus; Fatty Liver; Female; Glucose Intolerance	2010
Metformin: a therapeutic option for treating nonalcoholic fatty liver disease. Digestive diseases and sciences, 2010, Volume: 55, Issue:7 Topics: Diet; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatty Liver; Female; Follow-Up	2010
Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. Metabolism: clinical and experimental, 2011, Volume: 60, Issue:9 Topics: Adult; Aged; Arteries; Blood Flow Velocity; Blood Glucose; Fatty Liver; Female; Humans; Hypoglycemic	2011
Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA, 2011, Apr-27, Volume: 305, Issue:16 Topics: Adolescent; Alanine Transaminase; Antioxidants; Child; Double-Blind Method; Fatty Liver; Female; Hum	2011
Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: a 12-month randomized, prospective, open- label trial. Hepatology (Baltimore, Md.), 2011, Volume: 54, Issue:5 Topics: Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Biopsy; Drug Therapy, Combination;	2011
Discordant effects on central obesity, hepatic insulin resistance, and alanine aminotransferase of low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance. Diabetes, obesity & metabolism, 2012, Volume: 14, Issue:1 Topics: Alanine Transaminase; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Fatty Liver; Fema	2012
Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. Diabetologia, 2011, Volume: 54, Issue:12 Topics: Adult; Aged; Animals; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Therapy,	2011
Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. European journal of endocrinology, 2012, Volume: 166, Issue:3 Topics: Adult; alpha-2-HS-Glycoprotein; Biomarkers; Cross-Sectional Studies; Dose-Response Relationship, Dru	2012
Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering? Cardiovascular diabetology, 2012, Jun-07, Volume: 11 Topics: Adiponectin; Adult; Aged; Biomarkers; Blood Glucose; Down-Regulation; Fatty Liver; Female; Hemodynam	2012
Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes care, 2012, Volume: 35, Issue:7 Topics: Adult; Aged; Diabetes Mellitus, Type 2; Exercise; Fats; Fatty Acids, Monounsaturated; Fatty Liver; F	2012
Effect of insulin versus triple oral therapy on the progression of hepatic steatosis in type 2 diabetes. Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 2012, Volume: 60, Issue:7 Topics: Administration, Oral; Adult; Aged; Diabetes Mellitus, Type 2; Disease Progression; Fatty Liver; Fema	2012
Metformin superior to low‑fat diet for the treatment of patients with nonalcoholic fatty liver disease and/or steatohepatitis. Polskie Archiwum Medycyny Wewnetrznej, 2012, Volume: 122 Suppl 1 Topics: Adult; Diet, Fat-Restricted; Fatty Liver; Female; Humans; Male; Metformin; Middle Aged; Non-alcoholi	2012
Investigation of the effects of Chlorella vulgaris supplementation in patients with non-alcoholic fatty liver disease: a randomized clinical trial. Hepato-gastroenterology, 2012, Volume: 59, Issue:119 Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Antioxidants; Aspartate Aminotransferases;	2012
Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological treatment. A pilot study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2004, Volume: 36, Issue:6 Topics: Adult; Alanine Transaminase; Blood Flow Velocity; Diet; Fatty Liver; Female; Hemodynamics; Humans; H	2004
A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2005, Apr-01, Volume: 21, Issue:7 Topics: Adolescent; Blood Glucose; Child; Fatty Liver; Female; Humans; Hypoglycemic Agents; Insulin Resistan	2005
A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. The American journal of gastroenterology, 2005, Volume: 100, Issue:5 Topics: Adult; Aged; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biopsy; Body Mass Inde	2005
A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. The American journal of gastroenterology, 2005, Volume: 100, Issue:5 Topics: Adult; Aged; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biopsy; Body Mass Inde	2005
A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. The American journal of gastroenterology, 2005, Volume: 100, Issue:5 Topics: Adult; Aged; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biopsy; Body Mass Inde	2005
A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. The American journal of gastroenterology, 2005, Volume: 100, Issue:5 Topics: Adult; Aged; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biopsy; Body Mass Inde	2005
Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis. Alimentary pharmacology & therapeutics, 2008, Volume: 28, Issue:2 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Diet Therapy; Exercise Therapy; Fatty Live	2008

metformin and Fatty Liver

Research Excerpts

Research

Studies (166)

Authors

Clinical Trials (32)

Trial Overview

Trial Outcomes

Change in Body Composition

Change in Body Mass Index (BMI)

Change in Total Daily Dose of Insulin (TDI) Per kg

Change in Waist Circumference

Change in Blood Pressure

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Change in Serum Lipids

Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.

Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.

Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.

Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.

Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline

Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)

Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)

Change in Body Mass Index

Change in Nonalcoholic Fatty Liver Disease (NAFLD) Score (Histologic Feature Scores Determined by Standardized Scoring of Liver Biopsies) From Baseline at 96 Weeks of Treatment

Change in QOL- Psychosocial Health

Change in Quality of Life (QOL) Scores- Physical Health

Change in Serum Aspartate Aminotransferase (AST)

Change in Serum Vitamin E Levels

Number of Participants With Improvement in Ballooning Degradation Score

Number of Participants With Improvement in Liver Fibrosis Score

Number of Participants With Improvement in Lobular Inflammation Score

Number of Participants With Improvement in Steatosis Score

Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L

Hepatic Fat

Plasma Adipocytokines

Change in MRI-Proton Density Fat Fraction (MRI-PDFF)

Mean Fibrosis Score CAP™ (FibroMax)

Mean Transient Elastography Measurement (Fibroscan)

Reviews

Trials

Other Studies