Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease†

Background: The aim of the present study was to compare the effects of gliclazide, liraglutide, and metformin in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods: Eighty-seven subjects were randomized to receive liraglutide, metformin, or gliclazide for 24 weeks. Primary outcomes included HbA1c levels, intrahepatic fat (IHF) content, and liver function. Results: Both HbA1c levels and IHF content were reduced after treatment in all three groups. However, HbA1c levels were lower in the liraglutide- and metformin-treated groups than in the gliclazide-treated group, and reductions in IHF content were greater with liraglutide than with gliclazide. Liraglutide and metformin treatments reduced weight and improved liver function. Changes in IHF content were positively correlated with reductions in serum alanine aminotransferase and triglyceride levels, as well as weight. At 24 weeks, reductions in IHF content were greater in subjects with weight loss >= 5%, changes in waistline <= 0 cm (including decreases in waistline), HbA1c reductions >= 2.5%, and HbA1c levels <6.5%. Conclusions: In T2DM patients with NAFLD, compared with liraglutide and metformin, gliclazide resulted in less improvement in liver function, reductions in IHF content and HbA1c levels, and less weight loss; in addition, slightly better improvements were achieved with liraglutide than with metformin.