A phase 2 clinical trial of metformin as a treatment for non‐diabetic paediatric non‐alcoholic steatohepatitis

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Abstract
Summary: Background : Children with non‐alcoholic steatohepatitis are insulin‐resistant and metformin has been proposed as a potential therapy. However, paediatric safety and efficacy data are absent.Aim : To test the hypothesis that metformin therapy will safely improve markers of liver disease in paediatric non‐alcoholic steatohepatitis.Methods : Single‐arm open‐label pilot study of metformin 500 mg twice daily for 24 weeks in non‐diabetic children with biopsy‐proven non‐alcoholic steatohepatitis.Results : Ten obese children (mean body mass index 30.4) enrolled and completed the trial. Mean alanine aminotransferase and aspartate aminotransferase (AST) improved significantly (P < 0.01) from baseline (184, 114 U/L) to end of treatment (98, 68 U/L). Alanine aminotransferase normalized in 40% and AST normalized in 50% of subjects. Children demonstrated significant improvements in liver fat measured by magnetic resonance spectroscopy (30–23%, P < 0.01); insulin sensitivity measured by quantitative insulin sensitivity check index (0.294–0.310, P < 0.05); and quality of life measured by pediatric quality of life inventory 4.0 (69–81, P < 0.01).Conclusion : Open‐label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized‐controlled trial is needed to definitively determine the efficacy of metformin for paediatric non‐alcoholic steatohepatitis.