Objective: We aimed to compare the effectiveness of liraglutide vs. pioglitazone on hepatic fat liver disease; content and serum fetuin A levels in patients with type 2 diabetes mellitus and non-alcoholic Type 2 diabetes fatty liver disease. Methods: This was a single-center, open-label, prospective, and randomized trial using a parallel design and lasting 24 weeks. Sixty patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease were randomly assigned to the liraglutide and pioglitazone groups on a 1:1 basis using a computer-generated sequence. Fetuin-A levels were determined using enzyme-linked immunosorbent assay. Hepatic fat content was measured using proton H-1-MRS on a 1.5T whole-body MRI scanner. All analyses were performed with SPSS version 13.0. Results: In the liraglutide group, fetuin-A levels decreased after 24 weeks (666.1 +/- 109.4 vs. 443.7 +/- 90.5 mu g/mL, P<0.05). In the pioglitazone group, fetuin-A levels also decreased after 24 weeks (659.3 +/- 111.8 vs. 538.1 +/- 101.0 mu g/mL, P< 0.05) but not to the level of the liraglutide group. The liraglutide treatment resulted in a decrease in H-1-MRS (24.1 +/- 3.0 vs. 20.1 +/- 3.8, P <0.05). After 24 weeks, Delta Fetuin-A was positively correlated with Delta weight (r = 0.756, P=0.035), Delta BMI (r = 0.653, P=0.006), Delta waist circumference (r = 0.767, P=0.010), and Delta H-1-MRS (r= 0.732, P=0.004) in the liraglutide group. Conclusions: Liraglutide treatment resulted in a decrease in hepatic fat content and fetuin-A compared with pioglitazone treatment in patients with T2DM and NAFLD. Fetuin-A is positively correlated with weight and hepatic fat content. The reduction in the hepatic fat content may be attributed to weight loss rather than reduction of glucose. (C) 2020 Elsevier Masson SAS. Alt rights reserved.