From the Guidelines
Metformin is unlikely to cause liver disease, and it may even have beneficial effects on liver health in diabetic patients. While metformin is generally considered safe for the liver, there have been isolated case reports of metformin-induced hepatotoxicity, though these are extremely uncommon 1. In fact, metformin is often the preferred antidiabetic medication for patients with pre-existing liver disease, including non-alcoholic fatty liver disease (NAFLD), because it may actually improve liver function in many cases.
Key Points to Consider
- Metformin works by reducing insulin resistance and decreasing glucose production in the liver, which can have beneficial effects on liver health in diabetic patients 1.
- Regular liver function monitoring is recommended when starting any new medication, including metformin, but specific liver-related concerns should not typically prevent its use.
- If a patient experiences symptoms like unusual fatigue, abdominal pain, dark urine, or yellowing of the skin or eyes while taking metformin, they should contact their healthcare provider immediately, as these could indicate liver problems, though the cause would likely be something other than metformin.
Important Considerations
- Metformin should be used with caution in those with impaired hepatic function or heart failure because of the increased risk of lactic acidosis 1.
- Metformin may be temporarily discontinued before procedures including imaging studies using iodinated contrast, during hospitalizations, and when acute illness may compromise renal or liver function 1.
From the FDA Drug Label
Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.
Metformin and Liver Disease: Metformin may cause liver disease, as evidenced by reports of cholestatic, hepatocellular, and mixed hepatocellular liver injury in postmarketing use 2.
- Key Points:
- Liver injury has been reported with metformin use.
- The exact frequency and causal relationship are unclear due to voluntary reporting.
- Clinical Decision: Use metformin with caution, and monitor patients for signs of liver injury, especially in those with pre-existing hepatic impairment. 2
From the Research
Metformin and Liver Disease
- Metformin does not appear to cause or exacerbate liver injury, and it is often beneficial in patients with nonalcoholic fatty liver disease 3.
- Recent studies have shown that metformin has significant therapeutic benefits in various organ systems, particularly the liver, and it has positive effects on cirrhosis and anti-tumoral properties 4.
- Metformin can alleviate nonalcoholic fatty liver disease and cirrhosis, relieve liver damage, and reduce the incidence of hepatocellular carcinoma and cholangiocarcinoma 5.
Mechanisms and Effects
- The mechanisms underlying the clinical effects of metformin in treating nonalcoholic fatty liver disease are associated with liver glucose metabolism and the beneficial effects of metformin on this common liver disease 6.
- Metformin administration can reduce body mass index (BMI) and serum aspartate aminotransferase (AST) in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis 7.
- Metformin can also reduce body weight and has a marginal significant effect on serum alanine transaminase (ALT) in non-diabetic patients with non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis 7.
Safety and Efficacy
- The safety and efficacy of metformin use in liver diseases are still being debated, but the results are highly promising 4.
- Metformin has a good safety profile and relatively low cost, making it a potential treatment option for liver diseases 5.
- Further large-scale and well-designed randomized controlled trials are required to confirm the findings and establish the efficacy of metformin in treating liver diseases 7.