BACKGROUND: Nonalcoholic STEATOHEPATITIS (NASH) is a common liver disease that can progress to cirrhosis or hepatocellular carcinoma. It is estimated that up to 3% of the Iranian population have this condition. Although the pathogenesis of NASH is incompletely understood, there is signifi cant evidence pointing to the importance of insulin resistance. Metformin is an oral hypoglycemic agent known to improve insulin resistance. This study examines the effectiveness of metformin on biochemical and histological improvement among NASH patients in a randomized doubleblind controlled trial.METHODS: This study enrolled 33 biopsy-proven NASH patients. Other causes of liver disorders were excluded. Subjects were randomized to receive either metformin, 500 mg twice daily, or an identical-looking placebo. Overweight patients were also instructed to lose weight. Treatment continued for 6 months. Patients were regularly visited and liver enzyme levels recorded. Compliance and any adverse drug effects were recorded.RESULTS: In the metformin group, the mean aspartate aminotransferase (AST) level dropped from 61.2 IU/L to 32.7 IU/L and the mean alanine aminotransferase (ALT) level dropped from 85.1 IU/L to 50.8 IU/L. The mean AST level in the placebo group dropped from 54.3 IU/L to 37.9 IU/L, whereas the mean ALT level dropped from 111.8 IU/L to 55.4 IU/L in the placebo group. The decrease in liver enzymes was significant in both groups, but the magnitude of decrease was not significantly different.CONCLUSION: The improvement observed in liver enzyme levels is totally attributable to weight loss. Metformin had no significant effect on liver enzyme levels.