Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism

Abstract

Background : Pioglitazone is a promising therapeutic method for nonalcoholic steatohepatitis patients with or without type 2 diabetes. However, there is a remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone treatment in liver fat content in Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism.Methods : This is a secondary post hoc analysis of a previous randomized, parallel controlled, openlabel clinical trial (RCT)* with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The per protocol population (n= 184) was randomly divided into three groups: lifestyle intervention (LSI), LSI plus pioglitazone (PGZ) 15mg qd, and LSI plus BBR 0.5g tid, respectively, for 16 weeks. Proton magnetic resonance spectroscopy ( 1 H MRS) was used to assess liver fat content.Results : As compared with LSI, PGZ plus LSI treatment induced further decreased liver fat content in women [-8.26% (-17.18%, -0.65%), p = 0.025], but relatively increased liver fat content in men [9.79% (0.37%, 19.21%), p = 0.046]. There was a significant interaction between gender and efficacy of pioglitazone before ( p = 0.003) and after ( p = 0.011) adjustment for age, smoking, drinking, baseline BMI, BMI change, and treatment adherence. Conclusion : For Chinese NAFLD patients with abnormal glucose metabolism, pioglitazone treatment is recommended for women, but not for men, based on lifestyle interventions. * Trial registration: Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282. Registered 3 March 2008, https://register.clinicaltrials.gov.