Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available in vitro, in vivo and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.