From the Guidelines
Metformin generally does not damage kidney function in terms of eGFR, and it is considered safe for patients with mild to moderate kidney impairment (eGFR ≥30 mL/min/1.73m²). The medication is contraindicated in severe kidney disease (eGFR <30 mL/min/1.73m²) due to the risk of lactic acidosis, a rare but serious side effect 1. For patients with diabetes, metformin is typically started at 500 mg once or twice daily with meals, gradually increasing to an effective dose (usually 1000-2000 mg daily in divided doses) as tolerated.
Key Considerations
- Metformin should not be initiated for patients with an eGFR <45 mL/min/1.73 m2 1.
- The benefits and risks of continuing treatment should be reassessed when eGFR falls to <45 mL/min/1.73 m2 1.
- Metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in patients with eGFR 30–60 mL/min/1.73 m2 1.
- Regular kidney function monitoring is important for patients taking metformin, particularly those with existing kidney disease or risk factors for kidney impairment.
- Dose adjustments are recommended when eGFR falls below 45 mL/min/1.73m², with the dose halved when eGFR is between 30-44 mL/min/1.73m², and stopped when eGFR is <30 mL/min/1.73m² 1.
Monitoring and Follow-up
- 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.
- 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. 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)].
Metformin does not directly damage kidney function in terms of eGFR, but metformin is contraindicated in patients with severe renal impairment (eGFR below 30 mL/min/1.73 m^2) due to the increased risk of lactic acidosis.
- The risk of metformin accumulation and lactic acidosis increases with the severity of renal impairment.
- Renal function should be assessed prior to initiation of metformin and periodically thereafter.
- Metformin should be discontinued if the patient's eGFR falls below 30 mL/min/1.73 m^2 2.
From the Research
Metformin and Kidney Function
- Metformin is considered a safe option for patients with chronic kidney disease (CKD), as long as the dosage is adjusted individually 3, 4.
- The relationship between metformin levels and plasma lactate is not significant, even in patients with reduced kidney function 3.
- Metformin use has been associated with improved kidney outcomes, including a decreased likelihood of kidney events or death, compared to sulfonylureas 5, 6.
Estimated Glomerular Filtration Rate (eGFR)
- Metformin can be used safely in patients with mild to moderate CKD, defined by an eGFR of 30-60 mL/min per 1.73 m2 4.
- The risk of lactic acidosis is not substantially increased in patients with an eGFR of 30-60 mL/min per 1.73 m2 4.
- Metformin use has been associated with reduced mortality and improved cardiovascular outcomes in patients with CKD stage 4 and above 7.
Comparison with Sulfonylureas
- Metformin has been shown to be a safer alternative to sulfonylureas in patients with CKD, with a lower risk of all-cause mortality, cardiovascular events, and major hypoglycemic episodes 5, 6.
- The presence of CKD may attenuate the mortality benefit of metformin compared to sulfonylureas, but metformin is still considered a safer option 6.