Therapy of NAFLD: insulin sensitizing agents

Insulin resistance is an integral part of the underlying pathophysiology in most patients with nonalcoholic fatty liver disease (NAFLD). Insulin-sensitizing agents are therefore likely to be of key importance in the treatment of this disorder, especially in the histologically more severe form known as nonalcoholic steatohepatitis. Here we have reviewed the current literature on the two major insulin-sensitizing agents that have been studied in patients with NAFLD: the thiazolidinediones (or PPAR-gamma agonists) and metformin, the only available biguanide. Thiazolidinedione administration in human NAFLD has been shown to decrease hepatic fat by several different global measures and to decrease evidence of cellular injury, but it has also been associated with increased peripheral fat and weight gain. In contrast, metformin has been shown to improve biochemical markers without weight gain, but with more variable improvement in histology. Neither agent has been FDA approved for treating NAFLD, but existing studies have provided much hope for incorporating these medications into NAFLD management strategies in selected patients.