Further , in a cohort study of patients with type 2 diabetes , pioglitazone therapy was associated with a statistically significant decrease in the risk of all-cause mortality .
Despite these beneficial effects , the meta- analysis showed that pioglitazone therapy had higher risks of heart failure , bone fractures , edema and weight gain .
The low-dose pioglitazone therapy may show the same degree of improvements in glucose and lipid metabolism , fatty liver , insulin resistance , and adiponectin as the st and ard- and high-dose pioglitazone therapy .
Furthermore , the low-dose pioglitazone therapy may also show less adverse effects on weight gain , edema and heart failure as compared with the st and ard- and high-dose pioglitazone therapy
Pioglitazone is one of thiazolidinedione derivatives , which stimulates nuclear peroxisome proliferator-activated receptor gamma and improves glucose and lipid metabolism and insulin sensitivity .
A recent systematic review and meta- analysis showed that pioglitazone therapy was associated with a lower risk of major adverse cardiovascular events in patients with pre-diabetes and diabetes .
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis.
BACKGROUND No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis , which is characterized by insulin resistance , steatosis , and necroinflammation with or without centrilobular fibrosis . Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus . METHODS We r and omly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet  ( a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight ) plus pioglitazone ( 45 mg daily ) or a hypocaloric diet plus placebo . Before and after treatment , we assessed hepatic histologic features , hepatic fat content by means of magnetic resonance spectroscopy , and glucose turnover during an oral glucose tolerance test ( [14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion ) . RESULTS Diet plus pioglitazone , as compared with diet plus placebo , improved glycemic control and glucose tolerance ( P<0.001 ) , normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels ( by 40 % vs. 21 % , P=0.04 ) , decreased alanine aminotransferase levels ( by 58 % vs. 34 % , P<0.001 ) , decreased hepatic fat content ( by 54 % vs. 0 % , P<0.001 ) , and increased hepatic insulin sensitivity ( by 48 % vs. 14 % , P=0.008 ) . Administration of pioglitazone , as compared with placebo , was associated with improvement in histologic findings with regard to steatosis ( P=0.003 ) , ballooning necrosis ( P=0.02 ) , and inflammation ( P=0.008 ) . Subjects in the pioglitazone group had a greater reduction in necroinflammation ( 85 % vs. 38 % , P=0.001 ) , but the reduction in fibrosis did not differ significantly from that in the placebo group ( P=0.08 ) . Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone ; no other adverse events were observed . CONCLUSIONS In this proof-of-concept study , the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis . Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone . ( Clinical Trials.gov number , NCT00227110 [ Clinical Trials.gov ] . )
Further , in a cohort study of patients with type 2 diabetes , pioglitazone therapy was associated with a statistically significant decrease in the risk of all-cause mortality .
Despite these beneficial effects , the meta- analysis showed that pioglitazone therapy had higher risks of heart failure , bone fractures , edema and weight gain .
The low-dose pioglitazone therapy may show the same degree of improvements in glucose and lipid metabolism , fatty liver , insulin resistance , and adiponectin as the st and ard- and high-dose pioglitazone therapy .
Furthermore , the low-dose pioglitazone therapy may also show less adverse effects on weight gain , edema and heart failure as compared with the st and ard- and high-dose pioglitazone therapy
Pioglitazone is one of thiazolidinedione derivatives , which stimulates nuclear peroxisome proliferator-activated receptor gamma and improves glucose and lipid metabolism and insulin sensitivity .
A recent systematic review and meta- analysis showed that pioglitazone therapy was associated with a lower risk of major adverse cardiovascular events in patients with pre-diabetes and diabetes .