Patients with type 2 diabetes who received triple therapy (metformin/exenatide/pioglitazone) were found to have less hepatic steatosis and fibrosis at end-of-study (EOS) in comparison to those who underwent conventional therapy (metformin → glipizide → glargine insulin).

• In this study of 68 participants who completed the 6-year follow-up and had an end-of-study (EOS) FibroScan, the goal was to compare the efficacy of triple therapy vs stepwise conventional therapy on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes.

• Triple and conventional therapy groups had HbA1c value of 6.8% and 6.0%, respectively, at EOS.

• In conventional therapy vs triple therapy groups, grade 2/3 steatosis was present in 69% vs 31% of the patients, and stage 3/4 fibrosis was detected in 26% vs in 7% of the patients, respectively.

• More liver fat was detected in conventional therapy group vs triple therapy (12.9% vs 8.8%).

• Severity of hepatic steatosis and fibrosis were both found to be robustly and inversely correlated with insulin resistance.

• Triple therapy resulted in significant reductions in aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT), but only the reduction in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS.

• There appeared a limited value of liver fibrosis scores changes (APRI, NFS, Fibrosis-4, and AST/ALT ratio) in predicting treatment response.