From the Guidelines
Metformin should be discontinued when the estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73m². This recommendation is based on the most recent and highest quality study available, which suggests that the risk of metformin-associated lactic acidosis increases significantly at this level of kidney function 1.
Key Considerations
- For patients with an eGFR between 30-45 mL/min/1.73m², metformin can often be continued but with dose reduction (typically maximum 1000 mg daily) and careful monitoring.
- When eGFR is between 45-60 mL/min/1.73m², standard dosing can usually be maintained with regular kidney function monitoring.
- The reason for these restrictions is that metformin is primarily eliminated by the kidneys, and impaired kidney function leads to drug accumulation, increasing the risk of lactic acidosis, a rare but serious side effect.
- Patients with acute conditions that may worsen kidney function (severe infection, contrast dye procedures, major surgery) should temporarily stop metformin even if their baseline eGFR is above these thresholds.
- Regular kidney function monitoring is essential for all patients on metformin, with frequency increasing as eGFR decreases.
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.
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. Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2
Metformin should be stopped when the eGFR falls below 30 mL/minute/1.73 m^2 2.
- The drug is contraindicated in patients with an eGFR below this threshold.
- If the patient's eGFR later falls below 30 mL/minute/1.73 m^2, the drug should be discontinued.
From the Research
Metformin Use and GFR
- The decision to stop metformin due to reduced glomerular filtration rate (GFR) is based on various studies, including 3, which suggests that metformin should not be used at an eGFR less than 30 mL/min/1.73 m2.
- According to 4, metformin is mainly cleared by the kidneys, and its use is associated with a low risk of lactic acidosis, except in cases where patients have a concomitant disease or situation that reduces metformin renal clearance.
- A study published in 5 found that the risk of lactic acidosis hospitalization was uncommon and not statistically different between patients who continued metformin and those who continued sulfonylureas after developing reduced kidney function.
- Another study 6 found that metformin use was associated with an increased risk of acidosis only at eGFR less than 30 mL/min/1.73 m2, supporting cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2.
- A cohort study in Denmark and the UK 7 found that the incidence rates of lactic acidosis increased with decreasing baseline eGFR in both countries, but diagnosed lactic acidosis was rare and can occur regardless of renal function.
GFR Thresholds for Metformin Use
- The studies suggest the following GFR thresholds for metformin use:
- eGFR less than 30 mL/min/1.73 m2: metformin should not be used due to increased risk of lactic acidosis 3, 6.
- eGFR 30-44 mL/min/1.73 m2: metformin use is associated with a low risk of lactic acidosis, and its use can be considered with caution 3, 6.
- eGFR 45 mL/min/1.73 m2 or higher: metformin can be used with a low risk of lactic acidosis 3, 6.