While the use of vitamin E (Vit E) in nondiabetic patients with NASH has proven to be effective in the PIVENS study (NEJM 2010), there is no information about its effect in patients with NASH and T2DM. To examine this, we performed a randomized, double blind, controlled trial assessing the efficacy of Vit E, alone or combined with pioglitazone (PIO) in this population. Patients (n=105) were randomized 1:1:1 to Vit E 400 U BID, Vit E 400 U BID + PIO 45mg QD, or placebo for 18 months. The primary endpoint was histological improvement, defined as a 2-point reduction in the NAFLD activity score from 2 different parameters, without worsening of fibrosis. Secondary outcomes: resolution of NASH, individual histological scores, and metabolic parameters. Based on 2 planned primary comparisons, a p<0.025 was considered to indicate statistical significance. Groups were well matched at baseline. A total of 87 patients completed 18 months of follow-up. More patients on Vit E and PIO combination achieved the primary outcome compared to placebo (65% vs. 22%, p<0.001), but not in the Vit E alone group (36% vs. 22%, p=0.18). The same trend was observed for resolution of NASH, with a significant improvement only in the combination group (57% vs. 18%, p<0.001), but not with Vit E alone (42% vs. 18%, p=0.036). While steatosis grade improved with either combination (p<0.001) or Vit E alone (p=0.018), inflammation (p=0.018) and ballooning (p=0.022) grades only improved with Vit E + PIO. No improvement in fibrosis was observed in any group. Four patients died of cardiovascular causes during the study (2 on Vit E alone and 2 on combination). Weight gain, peripheral edema and hypoglycemia were more frequent in the combination group.
Conclusion: Vit E alone was ineffective to treat NASH in patients with T2DM. While the combination of Vit E and PIO was significantly better than placebo, response rate was similar to that reported for PIO alone in patients with T2DM, suggesting no role of Vit E in this population.
F. Bril: None. D.M. Biernacki: None. R. Lomonaco: None. S. Kalavalapalli: None. S.K. Subbarayan: None. J. Lai: None. F.O. Tio: None. A. Suman: None. B.K. Orsak: None. J. Hecht: None. K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc..