Article Summary Narrative Review: Hepatobiliary Disease in Type 2 Diabetes Mellitus. Tolman KG, Fonesca V, Tan MH, Dalpiaz A. Ann Intern Med. 2004;141:946-956. Objective: To identify the spectrum of liver disease that is now recognized as a major complication of type 2 diabetes, with the relative risk for mortality greater than for cardiovascular disease in this patient population. Methods: A MEDLINE search was conducted and included bibliographies of the citations of relevant articles, along with a search for reports of hepatotoxicity in the US Food and Drug Administration (FDA) Web site. Observation: The literature search produced 150 published articles reporting various discoveries, observations, and hypotheses relating to the metabolic effects and liver disorders associated with type 2 diabetes. The prevalence of nonalcoholic fatty liver disease is ≥50% in patients with type 2 diabetes and 100% in obese patients with diabetes. Fifty percent of affected patients have steatohepatitis and 19% have cirrhosis, although the pathogenesis is only partially understood. It is known, however, that insulin resistance and relative insulin deficiency do have an effect on the metabolism of carbohydrates and lipids. Other liver disorders that occur more frequently in patients with type 2 diabetes than in the general population include acute liver failure, cholelithiasis, hepatocellular carcinoma, and hepatitis C. This paper examines each of the liver conditions mentioned and reviews various treatment regimens available to patients with type 2 diabetes and liver disease, including lifestyle changes, foods with a low glycemic index, exercise, and pharmacotherapy. There are no current data indicating that patients with nonsevere liver disease have altered drug metabolism. Current recommendations include early treatment with an insulin secretagogue, with early transition to insulin if glycemic control is not rapidly achieved. Conclusion: All available classes of antihyperglycemic agents except the meglitinides and metformin have been associated with rare reports of hepatotoxicity. The prevalence of liver disease in this population makes treatment of type 2 diabetes extremely complex. New research is needed to determine the most efficacious treatment strategies.