A Randomized Controlled Trial of Metformin versus Vitamin E or Prescriptive Diet in Nonalcoholic Fatty Liver Disease

Bugianesi, Elisabetta; Gentilcore, Elena; Manini, R.; Natale, S.; Vanni, Ester; Villanova, Nicola; David, Ezio; Rizzetto, M.; Marchesini, Giulio

doi:10.1111/j.1572-0241.2005.41583.x

Cited by 635 publications

(480 citation statements)

References 34 publications

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“…107,108 An open-label trial consisting of 110 patients with NASH received either metformin 2 grams/day (55 patients), vitamin E 800 IU/day (28 patients) or dietary-induced weight loss (27 patients) for 12 months. 109 Aminotransferases improved more with metformin than with vitamin E or diet alone. However, there was only a modest improvement in hepatic steatosis and inflammation in the subset of 17 patients undergoing paired liver biopsies with metformin treatment.…”

Section: Metforminmentioning

confidence: 99%

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

et al. 2012

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Section: Metforminmentioning

confidence: 99%

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

et al. 2012

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“…Human studies have documented a reduction in aminotransferases with metformin. [6][7][8][9][10][11] However, alanine aminotransferase (ALT) breakthrough was reported, 12 suggesting that there is no sustained effect. Other 1-year trials showed no overall significant reduction in ALT values.…”

Section: Efficacy Outcomes In Nashmentioning

confidence: 99%

“…Two randomized trials showed no effect 8,14 on histology and one open-label trial showed improvement only in ballooning. 13 One study described histological improvement, 7 but the comparator arm did not undergo end-of-treatment biopsy, precluding definitive conclusions. These results could be due to metformin's weak antisteatogenic effect and no increase in adiponectin.…”

Section: Efficacy Outcomes In Nashmentioning

confidence: 99%

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

2010

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Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges for trial design and proposes endpoints for future proof of principle, registrational, and postmarketing trials. (HEPATOLOGY 2010;52:2206-2215 N onalcoholic steatohepatitis (NASH) is emerging as the next big therapeutic challenge in hepatology. 1 Currently the top cause of newly identified chronic liver diseases, NASH has potential for fibrosis, cirrhosis decompensation, and hepatocellular carcinoma. Not all individuals with metabolic risk factors will experience these adverse outcomes and identifying those at risk is critical. Prognostic markers for progression have mostly been derived from histological studies. Compared to steatosis alone or to steatosis and minimal inflammation, the coexistence of inflammation, cell injury (ballooning), and steatosis, a pathological aggregate labeled steatohepatitis, is associated with a significant increase in overall mortality and in liver-related mortality. The degree of inflammation is the best predictor of fibrosis progression, 2 a widely accepted surrogate for hard endpoints such as cirrhosis, endstage liver disease, and possibly hepatocellular carcinoma.Insulin resistance (IR) is consistently found in patients with NASH in both cross-sectional and longitudinal studies. Moreover, there is a stepwise increase in the severity of IR and its phenotypic complications (clustered as elements of the metabolic syndrome) between normal liver, isolated steatosis, and steatohepatitis that has prompted speculation that IR might contribute to liver damage. Logically, most therapeutic trials focused on insulin sensitizers (IS) as candidate therapies.The aim of this report is to critically review the results of trials of metformin and glitazones for NASH. We highlight methodological challenges for trial design and propose endpoints for future proof of principle, registrational, and postmarketing trials.

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“…Several uncontrolled studies using volunteers without diabetes showed improvement in ALT values, liver histology, or qualitative measurements of hepatic fatty infiltration (5)(6)(7)(8). The two randomized studies supporting the effectiveness of metformin in the treatment of NAFLD excluded patients with diabetes (9,10). In the only randomized trial that studied patients with type 2 diabetes, metformin was found to have a neutral effect on liver fat infiltration (11).…”

mentioning

confidence: 99%

Effect of insulin–metformin combination on hepatic steatosis in patients with type 2 diabetes

Lingvay¹,

Raskin²,

Szczepaniak³

2007

Journal of Diabetes and its Complications

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Objective-Hepatic steatosis occurs in up to 78% of patients with type 2 diabetes. Studies evaluating the effect of metformin on hepatic steatosis are conflicting. Insulin is believed to be detrimental due to its lipogenic effect. Since insulin and metformin combination is commonly used for the treatment diabetes, it is important to assess the effect of this combined therapy on hepatic steatosis. We evaluated the change in hepatic steatosis following initiation of insulin and metformin in patients with type 2 diabetes.Methods-Newly-diagnosed, treatment-naïve patients with type 2 diabetes had their hepatic triglyceride (TG) content measured by magnetic resonance spectroscopy at baseline and after 3 months of treatment with BiAsp 30 insulin in combination with metformin. Insulin was administered twice daily and titrated to achieve normal capillary blood glucose levels. Metformin was titrated during the first month from 500 mg daily to 1000 mg twice-daily.Results-The average hepatic TG content in the 19 subjects enrolled was 11.83%±7.61% (range 0.93% to 23.16%)] and correlated with BMI (r=0.567). Three months of treatment reduced hepatic steatosis by 45%, with 75% of the study subjects achieving a normal level. The change in hepatic TG content was partially explained by the change in HbA1c (p=0.006) and change in cholesterol level (p=0.003).Conclusions-The combined treatment with insulin and metformin reduced significantly hepatic steatosis in patients with newly-diagnosed type 2 diabetes. Keywords type 2 diabetes; hepatic steatosis; insulin treatment; metformin Non-alcoholic fatty liver disease (NAFLD) is characterized by fatty infiltration of the liver. This diagnosis represents a disease spectrum from simple steatosis to steatohepatitis. The prevalence of NAFLD has risen in the last decade parallel with the obesity and type 2 diabetes epidemics. (1). Previous studies suggest that one-third of the population has NAFLD (2). The prevalence of NAFLD in patients with type 2 diabetes is even higher. In the Dallas Heart Study,

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A Randomized Controlled Trial of Metformin versus Vitamin E or Prescriptive Diet in Nonalcoholic Fatty Liver Disease

Cited by 635 publications

References 34 publications

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

Effect of insulin–metformin combination on hepatic steatosis in patients with type 2 diabetes

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