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, because of the risk of lactic acidosis. This recommendation is based on the most recent and highest quality study available, which suggests that metformin can be safely used in patients with compensated cirrhosis, but with caution and close monitoring of liver and kidney function 1.
The use of metformin in patients with cirrhosis is a complex issue, and the risk of lactic acidosis is a major concern. Patients with advanced liver disease have impaired lactate clearance, which can lead to lactate accumulation when taking metformin. Additionally, cirrhotic patients often have compromised kidney function, which can further increase metformin levels and associated risks.
Key considerations for the use of metformin in patients with cirrhosis include:
- Compensated cirrhosis: Metformin can be used with caution in patients with compensated cirrhosis, but with close monitoring of liver and kidney function.
- Decompensated cirrhosis: Metformin is contraindicated in patients with decompensated cirrhosis, especially when there is concomitant renal impairment.
- Renal function: Metformin should be used with caution in patients with impaired renal function, and the dose should be adjusted accordingly.
- Monitoring: Regular monitoring of liver function, kidney function, and for signs of lactic acidosis is essential in patients with cirrhosis taking metformin.
Overall, the use of metformin in patients with cirrhosis requires careful consideration of the potential risks and benefits, and close monitoring of liver and kidney function. The most recent and highest quality studies available suggest that metformin can be safely used in patients with compensated cirrhosis, but with caution and close monitoring 1.
From the FDA Drug Label
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. [see Warnings and Precautions ( 5.1)] Hepatic impairment —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.
Metformin is not recommended for use in patients with hepatic impairment, including cirrhosis, due to the increased risk of lactic acidosis 2 2.
From the Research
Metformin Safety in Cirrhosis
- The safety of metformin in patients with 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, 5, 6, 7.
- 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 use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes, with no cases of metformin-associated lactic acidosis reported 4.
- A 2020 study found that the pharmacokinetics of metformin in patients with chronic liver disease are similar to those in patients with type 2 diabetes and no liver disease, and that metformin use is not associated with unsafe plasma lactate concentrations 5.
- However, a 2021 study found that metformin use is associated with a higher risk of metabolic acidosis in patients with Child-Pugh class B or C cirrhosis and stage 3A chronic kidney disease or above 6.
- A case report published in 2022 described a patient with normal kidney function and occult cirrhosis who developed metformin-associated lactic acidosis, highlighting the need for caution when using metformin in patients with cirrhosis, even if they have normal kidney function 7.
Key Findings
- Metformin may be safe to use in patients with cirrhosis, but caution is needed, particularly in those with advanced liver disease or chronic kidney disease 3, 4, 5, 6, 7.
- The risk of lactic acidosis associated with metformin use in patients with cirrhosis is a concern, particularly in those with Child-Pugh class B or C cirrhosis and stage 3A chronic kidney disease or above 6.
- Further research is needed to determine the safety of metformin in patients with cirrhosis and to identify factors that may increase the risk of lactic acidosis in these patients 3, 4, 5, 6, 7.