Body weight loss and glycemic control on the outcomes of patients with NAFLD. The role of new antidiabetic agents

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50-60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation. The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars. To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results. It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied. We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.