Efficacy of adding metformin to pegylated interferon and ribavirin in treatment naïve patients with chronic hepatitis C: a randomized double-blind controlled trial.

BACKGROUND Evidence indicates that insulin resistance results in poor sustained viral response (SVR) in patients with chronic hepatitis C (CHC). Metformin is an oral hypoglycemic agent which improves insulin resistance. METHODS We sought to determine if the addition of metformin to the treatment regimen could improve SVR in treatment-naïve CHC patients in a randomized, double-blind, placebo-controlled trial. We randomized 140 consecutive CHC patients to receive either metformin 500 mg three times a day or placebo in addition to pegylated interferon (PEG-IFN) and ribavirin (RBV). Only treatment-naïve subjects aged between 15 and 65 years of age were included. SVR was defined as no detectable HCV RNA six months after the end of treatment.Subjects who received at least one dose of PEG-IFN were included in the finala nalysis. RESULTS The SVR rate in the metformin group was 75% versus 79% in controls (intention-to-treat) which was not significantly different. Also, the difference between the placebo and metformin group was not significant in subsets of different genotypes or those with homeostasis model assessment of insulin resistance (HOMA-IR) levels greater than 2 or body mass index greater than 25. The most common complaint was gastrointestinal discomfort (13% in metformin group versus 4% in controls; p=0.002) that lead to discontinuation of metformin in 8 participants. CONCLUSION Although triple therapy with metformin, PEG-IFN and RBV is relatively well tolerated, the addition of metformin did not significantly improve viral response in CHC patients.