Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

Authors


  • As part of AP&T’s peer-review process, a technical check of this meta-analysis was performed by Dr. P. Collins.

Dr H. Conjeevaram, Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109, USA.
E-mail: omsairam@med.umich.edu

Abstract

Aliment Pharmacol Ther 2010; 32: 1211–1221

Summary

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.

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