From the Guidelines
Metformin can potentially cause lactic acidosis, a serious but rare condition involving buildup of lactic acid in the bloodstream, particularly in patients with compromised kidney or liver function, with an estimated incidence of approximately 3-10 cases per 100,000 patient-years of metformin use 1.
Key Points to Consider
- The medication works by decreasing glucose production in the liver and improving insulin sensitivity, but it can interfere with lactate metabolism, particularly in patients with kidney disease, liver disease, heart failure, severe infection, excessive alcohol intake, and dehydration.
- Symptoms of lactic acidosis include muscle pain, difficulty breathing, unusual sleepiness, stomach discomfort, and feeling cold, and if experienced, immediate medical attention should be sought.
- To minimize risk, metformin should be temporarily stopped before procedures using contrast dye, during severe illness, or if severe dehydration occurs, and regular kidney function monitoring is crucial for those on metformin therapy 1.
- Metformin may be safely used in individuals with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², while lower doses may be used in those with an eGFR 30–45 mL/min/1.73 m², and it is contraindicated in those with advanced renal insufficiency 1.
Important Considerations for Patient Care
- Regular monitoring of kidney function and eGFR is essential to minimize the risk of lactic acidosis.
- Patients should be educated on the symptoms of lactic acidosis and the importance of seeking immediate medical attention if they occur.
- Metformin should be used with caution in patients with hypoperfusion, hypoxemia, impaired hepatic function, or heart failure due to the increased risk of lactic acidosis 1.
From the FDA Drug Label
Metformin, the active ingredient in metformin hydrochloride tablets, can cause a rare but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk.
Yes, metformin can cause a buildup of lactic acid, a condition known as lactic acidosis, especially in patients with certain risk factors such as renal impairment, liver problems, or those who drink alcohol very often 2.
From the Research
Metformin and Lactic Acid Buildup
- Metformin is known to facilitate the production of lactate, and predisposing factors can accelerate this process, leading to lactic acidosis 3.
- The relationship between metformin and lactic acidosis is complex, and metformin may be causal, co-responsible, or coincidental in the development of lactic acidosis 4.
- Lactic acidosis associated with metformin treatment is a rare but important adverse event, and the incidence is low 4, 5.
Risk Factors for Lactic Acidosis
- Renal impairment, liver disease, heart failure, and other metabolic disturbances can increase the risk of lactic acidosis in patients taking metformin 3, 5, 6, 7.
- Situations such as infection, dehydration, and acute kidney insufficiency can also increase the risk of lactic acidosis 3, 6.
- Patients with chronic nephropathy are at a higher risk of developing lactic acidosis due to reduced metformin renal clearance 6.
Management and Prevention
- Haemodialysis or continuous renal replacement therapy (CRRT) can be effective in managing severe lactic acidosis by eliminating lactate and metformin 4, 6, 7.
- Temporarily discontinuing metformin in situations where the risk of lactic acidosis is increased, such as severe infection, dehydration, and acute kidney insufficiency, can help prevent the development of lactic acidosis 3, 6.
- Awareness and education among patients and clinicians are crucial in preventing and managing metformin-associated lactic acidosis 3, 6, 7.