From the Guidelines
Metformin should be held in patients with acute liver failure. While metformin is primarily eliminated by the kidneys rather than metabolized by the liver, acute liver failure often leads to multi-organ dysfunction including kidney injury, lactic acidosis, and hemodynamic instability, as noted in a study published in The Lancet Diabetes and Endocrinology 1. Metformin can accumulate in the setting of renal dysfunction and may worsen lactic acidosis, which is already a concern in liver failure.
Some key points to consider in the management of patients with acute liver failure include:
- Monitoring blood glucose closely
- Using alternative glucose-lowering strategies such as insulin therapy if needed
- Making careful dose adjustments based on frequent glucose monitoring
- Avoiding metformin in patients at risk for lactic acidosis, such as those with impaired lactic acid clearance (liver failure) 1
- Discontinuing metformin if the estimated glomerular filtration rate (eGFR) is less than 30 mL/min per 1.73 m², as recommended in the study 1
Metformin therapy can be reconsidered once the patient has recovered from acute liver failure and both liver and kidney function have stabilized. The decision to restart metformin should be based on a comprehensive assessment of the patient's organ function and overall clinical status, taking into account the potential risks and benefits of metformin therapy, as discussed in the study published in The Lancet Diabetes and Endocrinology 1.
From the FDA Drug Label
Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. 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 should be held in acute liver failure because the drug may increase the risk of lactic acidosis in patients with hepatic impairment, and its use is not recommended in such cases 2, 2.
- The risk of metformin-associated lactic acidosis increases in patients with hepatic impairment.
- Metformin hydrochloride tablets are not recommended in patients with hepatic impairment due to the associated risk of lactic acidosis.
From the Research
Metformin Use in Acute Liver Failure
- Metformin is generally considered safe, but it can be associated with lactic acidosis, a rare but serious side effect 3, 4.
- The risk of lactic acidosis is higher in patients with renal failure and liver disease 3, 4, 5.
- In cases of acute liver failure, the use of metformin may be complicated by the development of lactic acidosis 4, 6.
- The liver plays a key role in lactate clearance, and liver failure can increase the risk of lactic acidosis 3, 7.
Management of Metformin in Acute Liver Failure
- Haemodialysis is recommended in severe cases of lactic acidosis to eliminate lactate and metformin 3, 5, 6.
- The decision to hold metformin in acute liver failure should be based on the individual patient's risk factors and the severity of the liver disease 7, 4.
- Patients with cirrhosis, particularly those with encephalopathy, may be at higher risk of developing lactic acidosis and should be monitored closely 7, 4.
Key Considerations
- Metformin does not appear to cause or exacerbate liver injury, and it may be beneficial in patients with nonalcoholic fatty liver disease 7.
- The relationship between metformin accumulation and lactic acidosis is complex, and plasma metformin levels do not reliably correlate with the severity of lactic acidosis 5, 6.
- Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality 5, 6.