Clarifying metformin's role and risks in liver dysfunction.

OBJECTIVES: To explore why some clinicians hesitate to use metformin in patients with liver disease and whether routine monitoring of transaminases before and during metformin therapy is substantiated. DATA SOURCES: A Medline literature search was conducted (1966 to June 2008) using the terms metformin, lactic acidosis, liver disease, chronic liver disease, hepatotoxicity, hypoxia, risks, and predisposing factors. DATA SYNTHESIS: Manufacturer prescribing information and some current medical and lay press literature caution against metformin use in patients with liver disease. This recommendation is interpreted variably by different prescribers, with some believing that the caution implies metformin can cause or worsen liver injury. Others believe that liver disease predisposes patients to developing lactic acidosis. A clearer understanding of how and when to screen for liver dysfunction in patients before and during metformin therapy is thus warranted.
CONCLUSION: Metformin does not appear to cause or exacerbate liver injury and, indeed, is often beneficial in patients with nonalcoholic fatty liver disease. Nonalcoholic fatty liver frequently presents with transaminase elevations but should not be considered a contraindication to metformin use. Literature evidence of liver disease being associated with metformin-associated metabolic acidosis is largely represented by case reports. Most such patients had cirrhosis and were also actively using alcohol. Patients with cirrhosis, particularly those with encephalopathy, may have arterial hypoxemia, which heightens the risk of developing lactic acidosis. For this reason, identifying patients with cirrhosis before initiating metformin seems prudent. Because cirrhosis can exist in the face of normal liver transaminases, however, and because metformin is not considered intrinsically hepatotoxic, withholding metformin from patients with abnormal transaminases or routinely monitoring transaminases before or during metformin treatment is not supported.