From the Guidelines
Metformin should not be used in patients with severe kidney disease (eGFR below 30 mL/min/1.73m²), acute or chronic metabolic acidosis including diabetic ketoacidosis, and severe liver disease, as stated in the most recent guidelines 1.
Key Contraindications
- Severe kidney disease (eGFR below 30 mL/min/1.73m²)
- Acute or chronic metabolic acidosis including diabetic ketoacidosis
- Severe liver disease
- Acute heart failure, respiratory failure, or any hypoxic state due to increased risk of lactic acidosis
- History of metformin-associated lactic acidosis or hypersensitivity to metformin
Precautions and Temporary Discontinuation
- 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.
- Patients with impaired hepatic function or heart failure should use metformin with caution due to the increased risk of lactic acidosis.
- Monitoring for vitamin B12 deficiency should be considered for those taking metformin long-term 1.
Rationale
The contraindications and precautions for metformin use are primarily due to the increased risk of lactic acidosis, a rare but serious side effect with high mortality 1. Metformin is primarily eliminated by the kidneys, and impaired kidney function can lead to drug accumulation and increased risk of lactic acidosis. In patients with liver disease, the liver cannot clear lactate effectively, further increasing lactic acidosis risk. During periods of tissue hypoxia, lactic acid production naturally increases, which can be exacerbated by metformin.
From the FDA Drug Label
4 CONTRAINDICATIONS Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m2) [see Warnings and Precautions (5.1)]. Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
The contraindications for metformin are:
- Severe renal impairment (eGFR below 30 mL/min/1.73 m2)
- Hypersensitivity to metformin
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma 2
From the Research
Metformin Contraindications
- Metformin is contraindicated in individuals with impaired kidney function due to concerns of lactic acidosis 3, 4, 5.
- The risk of lactic acidosis associated with metformin use in individuals with impaired kidney function is a significant concern, with a mortality rate approaching 50% 5.
- Metformin is generally contraindicated in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73m2) due to increased risk of lactic acidosis and all-cause mortality 4, 6.
- However, some studies suggest that metformin may be safely used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rate 30-60 mL/min/1.73m2) with appropriate dosage reductions and careful follow-up of kidney function 3, 4, 7.
Specific Contraindications
- Severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73m2) 4, 6.
- Acute renal deterioration 7.
- Concomitant diseases or situations that reduce metformin renal clearance, such as sepsis, fever, diarrhea, vomiting 7.
- High daily dose (>2 g) of metformin in patients with impaired renal function 6.
- Cumulative dose of ≥730 g of metformin in the preceding year in patients with impaired renal function 6.
Precautions
- Patients with mild to moderate chronic kidney disease should be closely monitored for signs of lactic acidosis and kidney function should be regularly assessed 3, 4, 7.
- Metformin dosage should be adjusted or discontinued if renal function falls below 60 mL/min/1.73m2 6.
- Patients should be aware of the risks of lactic acidosis and the importance of discontinuing metformin in case of concomitant diseases or situations that reduce metformin renal clearance 7.