The effect of metformin on the efficacy of antiviral therapy in patients with genotype 1 chronic hepatitis C and insulin resistance

Objectives: Insulin resistance (IR) affects sustained virological response (SVR) in chronic hepatitis C (CHC). The aim of this study was to investigate the effect of adding metformin to peginterferon alfa-2a and ribavirin on the efficacy in patients with genotype 1 CHC and IR. Methods: Ninety-eight patients with genotype 1 CHC and IR were randomized into the treatment group (n = 49) and the control group (n = 49). Patients in the control group received peginterferon alfa-2a and ribavirin, and patients in the treatment group received metformin in addition to peginterferon alfa-2a and ribavirin. The rate of virological response, changes in the homeostasis model assessment of insulin resistance (HOMA-IR) index, and the incidence of side effects were compared between the two groups. Factors influencing the SVR were studied by multivariate analysis. Results: The SVR rate of the treatment group was significantly higher than that of the control group (59.2%, 29/49 vs. 38.8%, 19/49; Chi-square = 4.083, p = 0.043). The HOMA-IR index of patients in the treatment group was lower than that of patients in the control group at weeks 12, 24, and 48 of the treatment period, and at week 24 of follow-up (3.00 +/- 0.65 vs. 3.50 +/- 0.72, 1.90 +/- 0.45 vs. 2.90 +/- 0.64, 1.75 +/- 0.40 vs. 2.74 +/- 0.48, and 1.60 +/- 0.35 vs. 2.60 +/- 0.55, respectively; t = 3.610, 8.947, 11.091, and 10.738, respectively; p < 0.01). Diarrhea was more often seen in the treatment group (28.6%, 14/49 vs. 10.2%, 5/49; Chi-square = 5.288, p = 0.021). In the multivariate logistic regression analysis, the independent factors associated with SVR were treatment method (p = 0.009) and HOMA-IR < 2 at week 24 (p = 0.011). Conclusions: A combination of metformin, peginterferon alfa-2a, and ribavirin improved insulin sensitivity and increased the SVR rate of patients with hepatitis C genotype 1 and IR, with a good safety profile. (C) 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.