Clarifying metformin's role and risks in liver dysfunction

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.