Is metformin safe to use in patients with liver cirrhosis?

From the Guidelines

Metformin can be used in adults with compensated cirrhosis and preserved renal function, but should not be used in adults with decompensated cirrhosis, especially when there is concomitant renal impairment, due to the risk of lactic acidosis. This recommendation is based on the latest guidelines from the Journal of Hepatology, 1. When using metformin in patients with liver cirrhosis, it is essential to consider the following:

• The patient should have compensated cirrhosis, as metformin is contraindicated in decompensated cirrhosis
• The patient should have preserved renal function, as renal impairment increases the risk of lactic acidosis
• Regular monitoring of liver function and renal function is crucial, with tests recommended every 3-6 months
• The dose of metformin should be adjusted according to the patient's renal function and glycemic response
• Alternative diabetes medications like GLP-1 receptor agonists or SGLT2 inhibitors may be safer options for patients with decompensated cirrhosis or renal impairment, as suggested by the guidelines 1. The risk of metformin-associated lactic acidosis is increased in individuals with renal impairment and hepatic decompensation, especially when both are present, as noted in the guidelines 1. Therefore, it is crucial to carefully evaluate the patient's condition and adjust the treatment plan accordingly.

From the FDA Drug Label

Patients with hepatic impairment have developed cases of metformin- associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels Therefore, avoid use of metformin hydrochloride tablets in patients with clinical or laboratory evidence of hepatic disease. Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. Metformin hydrochloride tablets are not recommended in patients with hepatic impairment.

Metformin is not safe to use in patients with liver cirrhosis, as it may increase the risk of lactic acidosis due to impaired lactate clearance.

• The FDA drug label recommends avoiding the use of metformin in patients with clinical or laboratory evidence of hepatic disease 2 2.
• Patients with liver cirrhosis should not be prescribed metformin due to the increased risk of lactic acidosis.

From the Research

Metformin Safety in Liver Cirrhosis

• The safety of metformin in patients with liver cirrhosis is a topic of debate, with some studies suggesting that it can be used safely in these patients, while others raise concerns about the risk of lactic acidosis 3, 4.
• A study published in 2010 found that metformin does not appear to cause or exacerbate liver injury and may be beneficial in patients with nonalcoholic fatty liver disease 3.
• Another study published in 2014 found that continuation of metformin after a diagnosis of cirrhosis significantly improves survival of patients with diabetes, with no cases of metformin-associated lactic acidosis reported 4.
• However, a case report published in 2022 described a patient with occult cirrhosis who developed severe lactic acidosis while taking metformin, highlighting the potential risks of metformin use in patients with liver disease 5.
• A review of the literature on lactic acidosis induced by metformin found that the risk of this complication is rare, but may be increased in patients with liver disease, particularly those with cirrhosis 6.
• A study published in 2022 found that metformin use was associated with higher risks of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis, particularly those taking high doses of the medication 7.

Key Findings

• Metformin may be safe to use in patients with liver cirrhosis, but the risk of lactic acidosis should be carefully considered 3, 4.
• The decision to use metformin in patients with liver cirrhosis should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 6.
• High doses of metformin may increase the risk of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis 7.
• Further research is needed to fully understand the safety and efficacy of metformin in patients with liver cirrhosis 4, 7.