From the Guidelines
Metformin use is associated with lactic acidosis, which can lead to acute kidney injury (AKI), and the risk of lactic acidosis is very low in absolute terms, but increases when the estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m². Metformin can accumulate in the body when kidney function is impaired, leading to increased lactate production and decreased lactate clearance. The condition is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH (<7.35), and electrolyte disturbances. Risk factors include pre-existing kidney disease, dehydration, sepsis, liver disease, and concomitant use of nephrotoxic medications.
Key Considerations
- Metformin may cause vitamin B12 deficiency, and monitoring of levels is advised with long-term use (>4 years) 1.
- The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extended-release formulation 1.
- Metformin is cleared by kidney filtration, and metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m² 1.
Recommendations
- Regular monitoring of kidney function is essential for patients on metformin, with dose adjustments or discontinuation recommended when estimated glomerular filtration rate (eGFR) falls below 45 ml/min/1.73m², and contraindicated when eGFR is below 30 ml/min/1.73m² 1.
- Metformin should be temporarily discontinued in situations that may compromise kidney function, such as during acute illness, severe infection, or when undergoing procedures requiring iodinated contrast 1.
From the FDA Drug Label
Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment
The type of renal failure associated with metformin use is not explicitly stated in the drug label, but it is mentioned that metformin accumulation and lactic acidosis increases with the severity of renal impairment. The label also mentions that metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m^2, indicating a risk of lactic acidosis in patients with severe renal impairment.
- Key points:
From the Research
Metformin-Associated Renal Failure
- Metformin use has been associated with an increased risk of acute kidney injury (AKI) and lactic acidosis, particularly in patients with pre-existing kidney disease 3, 4, 5, 6.
- The type of renal failure most commonly associated with metformin use is acute tubular necrosis, which can lead to severe acute renal failure 3.
- Metformin-induced lactic acidosis with AKI is rare but well-known, and the development of metformin-induced AKI should be considered for patients with several AKI risk factors who are taking metformin 3, 4, 5.
- Some studies suggest that metformin may have an adverse effect on renal function in patients with type 2 diabetes mellitus and moderate chronic kidney disease (CKD) 7.
- The risk of lactic acidosis associated with metformin use in individuals with impaired kidney function is generally considered to be low, but it can be increased in patients with severe kidney disease or those taking other medications that affect kidney function 4, 5.
Key Factors Contributing to Metformin-Associated Renal Failure
- High levels of metformin, which can accumulate in patients with impaired kidney function 3, 5, 6.
- Pre-existing kidney disease, such as CKD or acute kidney injury 3, 4, 7, 5, 6.
- Concomitant use of other medications that affect kidney function, such as angiotensin receptor blockers or SGLT2 inhibitors 3.
- Dehydration, alcohol consumption, or other factors that can reduce metformin renal clearance 3, 5.