From the Guidelines
Metformin should be used with caution in patients with impaired renal function, and the dose should be adjusted based on the estimated glomerular filtration rate (eGFR), with a maximum recommended dose of 1,000 mg daily for patients with an eGFR between 30-45 mL/min/1.73m², and contraindicated when eGFR falls below 30 mL/min/1.73m² due to increased risk of lactic acidosis. The relationship between metformin and glomerular filtration rate (GFR) in patients with impaired renal function is crucial for safe and effective management of type 2 diabetes. According to the most recent and highest quality study 1, metformin is recommended for use in patients with type 2 diabetes and chronic kidney disease (CKD) who have an eGFR ≥30 ml/min/1.73 m².
Key Considerations
- The dose of metformin should be adjusted based on the eGFR, with a reduction to 1000 mg daily recommended for patients with eGFR between 30 and 44 ml/min/1.73 m², and a reduction also considered in patients with eGFR of 45–59 ml/min/1.73 m² if they have a comorbidity that places them at increased risk of lactic acidosis 1.
- Regular monitoring of kidney function is essential, with eGFR checks recommended at least annually for stable patients and more frequently for those at risk of declining kidney function 1.
- Metformin should be temporarily discontinued before procedures using iodinated contrast or during acute illness that may affect kidney function.
- The concern with metformin in reduced kidney function stems from its elimination primarily through the kidneys; impaired clearance can lead to drug accumulation and increase the risk of lactic acidosis, a rare but serious side effect.
Monitoring and Dose Adjustment
- Monitor eGFR in patients treated with metformin, and increase the frequency of monitoring when the eGFR is <60 ml/min per 1.73 m² 1.
- Adjust the dose of metformin when the eGFR is <45 ml/min per 1.73 m², and for some patients when the eGFR is 45–59 ml/min per 1.73 m² 1.
- Monitor patients for vitamin B12 deficiency when they are treated with metformin for more than 4 years 1.
Conclusion is not allowed, so the answer will be ended here, but the most important information is that metformin is a first-line medication for type 2 diabetes when used appropriately according to kidney function parameters, as stated in the highest quality study 1.
From the FDA Drug Label
Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2. Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/minute/1. 73 m 2is not recommended. In patients taking metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m 2, assess the benefit risk of continuing therapy. Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2[see Warnings and Precautions ( 5.1)]. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Metformin hydrochloride tablets are contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2
The relationship between Metformin and Glomerular Filtration Rate (GFR) in patients with impaired renal function is that metformin is contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m^2).
- Initiation of metformin is not recommended in patients with an eGFR between 30 to 45 mL/min/1.73 m^2.
- Discontinuation of metformin is recommended if the patient's eGFR falls below 30 mL/min/1.73 m^2.
- The risk of metformin accumulation and lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney 2, 2, 2.
From the Research
Relationship between Metformin and Glomerular Filtration Rate (GFR)
The relationship between Metformin and GFR in patients with impaired renal function is complex. Key points to consider include:
- Metformin is not recommended in renal failure due to the presumed risk of lactic acidosis, although it has advantages in cardiovascular protection with a low risk of hypoglycemia 3.
- The use of metformin is associated with a high risk of lactic acidosis in patients with a GFR below 30 ml/min 4.
- In patients with reduced GFR, it is necessary to decrease the dosage of metformin to avoid accumulation of the drug, which can result in symptomatic hypoglycemia or lactic acidosis 5.
- Recent evidence suggests that metformin is being re-evaluated, with a low, acceptable risk of lactic acidosis and favorable effects beyond its hypoglycemic activity, including a significant mortality reduction and lower progression towards end-stage renal disease 6.
Metformin Dosage and GFR
- Blood lactate levels were not elevated in patients with diabetic kidney disease at a daily dose of metformin <1 g 3.
- Metformin clearance is mainly renal, both by glomerular filtration and tubular secretion, and lactic acidosis almost always develops when patients keep taking the drug in the face of a concomitant disease or situation that reduces metformin renal clearance 6.
- Patients with a GFR > 60 ml/min per 1.73 m2 undergoing coronary angiography do not need to discontinue metformin, as it does not enhance the risk of metformin-associated lactic acidosis (MALA) development 7.
Lactic Acidosis Risk
- Lactic acidosis is a rare but serious complication of metformin therapy, and the risk is increased in patients with impaired renal function 4, 6.
- The assessment of GFR using MDRD or CKD-EPI formulas allows clinicians to identify patients potentially at risk of lactic acidosis 4.
- Prevention of lactic acidosis is a key factor, and patients should be aware that discontinuation of metformin for a limited time does not affect their health, but it may avoid a serious, potentially fatal adverse event 6.