Aliment Pharmacol Ther 2010; 32: 1211–1221

Background  Non‐alcoholic fatty liver disease generally has a benign course; however, patients with non‐alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.

Aim  To assess the efficacy of insulin‐sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy‐proven NASH.

Methods  Multiple online databases and conference abstracts were searched. Random effects meta‐analyses were performed, with assessment for heterogeneity and publication bias.

Results  Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P < 0.001), but not inflammation (P = 0.09) or fibrosis (P = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P = 0.008). Metformin failed to improve any pooled outcome.

Conclusions  Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long‐term outcomes of glitazone therapy in patients without diabetes.