Pepa GD, Russo M, Vitale M, et al. - Since non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) share pathophysiological mechanisms and possible therapeutic strategies, researchers sought to assess the impacts of 1-year treatment with pioglitazone or sulphonylureas on indirect indices of NAFLD in people with T2D and the role of insulin-resistance and glucotoxicity in determining these effects. Patients with T2D (n = 195) aged 50-75 years who were poorly controlled with metformin 2 g/day were randomly allocated to add-on pioglitazone (n = 98) or sulphonylureas (n = 97) within the TOSCA.IT trial. One-year treatment with pioglitazone, even at low doses, improved liver steatosis and inflammation, as well as systemic and adipose tissue insulin resistance in T2D patients. The advantageous impacts of pioglitazone on NAFLD were independent of blood glucose control.