The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Department of Gastroenterology, Naval Medical Center San Diego, San Diego, CA, USA .
Therapeutic Advances in Gastroenterology 05/2009; 2(3):157-63. DOI: 10.1177/1756283X09105462
Source: PubMed

ABSTRACT Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n ¼10) or group B (n¼ 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations.
    06/2012; 2(2):156-173. DOI:10.1016/S0973-6883(12)60104-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Paediatric nonalcoholic fatty liver disease (NAFLD) is a major public health concern given the recent increase in its prevalence and link to obesity and other metabolic comorbidities. Current treatment strategies involve lifestyle changes. Other surgical and pharmacologic interventions have been proposed; however, limited randomised controlled trials (RCTs) in the paediatric population restrict their use.AimTo review the current management of paediatric NAFLD, including lifestyle and pharmacologic interventions, and to formulate recommendations for study design for future studies.MethodsA MEDLINE, Pubmed and Cochrane Review database search used a combination of keywords, including NAFLD, nonalcoholic steatohepatitis (NASH), paediatric, treatments, lifestyle changes, bariatric surgery, orlistat, metformin, thiazolidinediones, vitamin E, cysteamine bitartrate, ursodeoxycholic acid (UDCA), probiotics, omega-3 fatty acids, pentoxyfylline, farnesoid X receptor agonist and toll-like receptor modifiers. The articles were selected based on their relevance to the review.ResultsLifestyle interventions involving diet and exercise remain first-line treatment for paediatric NAFLD. Bariatric surgery, orlistat, insulin sensitisers and UDCA have been evaluated but are not recommended as first or second-line therapy. Medications such as cysteamine bitartrate, probiotics, polyunsaturated fats and pentoxyfilline share beneficial effects in trials, however, there is a paucity of adequately powered RCTs in which liver histology is evaluated. Vitamin E has been shown to be effective and safe in improving NASH histology in children.Conclusions Lifestyle intervention should be first-line treatment for paediatric NAFLD. Vitamin E should be considered for those with biopsy-proven NASH or borderline NASH failing first-line therapy. Other therapeutics show promising results but require larger RCTs with convincing endpoints. Improved screening techniques, objective validated inclusion criteria and outcome measures as well as rigour in study design are necessary for propelling therapeutic discovery.
    Alimentary Pharmacology & Therapeutics 09/2014; 40(10). DOI:10.1111/apt.12972 · 4.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.
    World Journal of Gastroenterology 09/2014; 20(34):12082-12101. DOI:10.3748/wjg.v20.i34.12082 · 2.43 Impact Factor

Full-text (2 Sources)

Available from
Aug 19, 2014