1047 Changes in Liver Fibrosis Scores in Patients With New Onset Type 2 Diabetes on Triple Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy: Year Two Results

Abstract

INTRODUCTION: Patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are at higher risk of developing advanced fibrosis. Certain diabetes medications such as pioglitazone and GLP1 agonists have shown some efficacy against NAFLD in small clinical trials. The Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM trial is an ongoing interventional trial assessing the effects of two different approaches to treating T2D (ClinicalTrials.gov Identifier: NCT01107717). The aim of the current study was to evaluate the effects of these two approaches on liver fibrosis scores after two years of treatment. METHODS: Newly diagnosed, drug-naïve T2DM patients were enrolled into the study. Medical history, clinical characteristics were obtained, and blood was drawn for the measurement of plasma glucose concentration, HbA1c, CBC, and blood chemistries. Subjects were randomized to receive in an open label fashion an initial combination therapy with metformin (2000 mg) plus pioglitazone (45 mg) and exenatide 10 µg BID (triple therapy) or sequential addition of metformin followed by sulfonylurea and insulin (conventional therapy) to maintain HbA1c < 6.5%. Subjects were seen every 3 months for follow-up visits and at 2 years all baseline measurements were repeated. Liver fibrosis scores that were calculated included AST/ALT ration, APRI, FIB-4 and NFS. RESULTS: Baseline characteristics are listed in Table 1; patients were well matched. Liver fibrosis scores at baseline and at 2 years are listed in Table 2. To compare the effect of each therapy on liver fibrosis scores, the ratio between the 2-year values of liver fibrosis scores to the baseline values was compared amongst the two treatment groups with ANOVA. Both therapies significantly reduced liver fibrosis scores but no significant difference was noted between the two treatment arms. CONCLUSION: In this randomized trial in patients with new-onset T2D, good control of HbA1c was associated with reduction in liver fibrosis scores at 2 years but the use of pioglitazone and GLP1 agonist did not have an added benefit over conventional therapy. The effects of longer duration of treatment are currently being evaluated in addition to assessment of fibrosis by Fibroscan and MR elastography.