What is the cutoff for metformin use based on Glomerular Filtration Rate (GFR)?

From the Guidelines

Metformin should be discontinued when the estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73m². For patients with an eGFR between 30-45 mL/min/1.73m², metformin can be used with caution at reduced doses, with close monitoring of kidney function. When eGFR is 45-60 mL/min/1.73m², metformin can generally be continued with regular kidney function monitoring every 3-6 months. No dose adjustment is needed for patients with eGFR above 60 mL/min/1.73m².

Key Considerations

• Metformin is primarily eliminated by the kidneys, and impaired kidney function can lead to drug accumulation, increasing the risk of lactic acidosis, a rare but serious side effect.
• Patients with declining kidney function should be monitored more frequently, and those with acute conditions that may worsen kidney function (severe infection, dehydration, contrast dye procedures) may need temporary metformin discontinuation even if their baseline eGFR is above the cutoff.
• The KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease recommends treating patients with T2D, CKD, and an eGFR ≥30 ml/min per 1.73 m² with metformin 1.
• Monitoring of eGFR is crucial in patients treated with metformin, and the dose should be adjusted accordingly 1.

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.
• 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.
• Consider dose reduction in certain conditions, such as high risk for acute kidney injury.
• The suggested approach to dosing metformin based on the level of kidney function is outlined in Figure 27 of the KDIGO 2022 guideline 1.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.

The cutoff for metformin use based on Glomerular Filtration Rate (GFR) is:

• Contraindicated: eGFR less than 30 mL/min/1.73 m^2
• Not recommended to initiate: eGFR between 30 to 45 mL/min/1.73 m^2
• Assess benefit and risk of continuing therapy: eGFR falls below 45 mL/min/1.73 m^2 2 2

From the Research

Metformin Use and Glomerular Filtration Rate (GFR)

• The use of metformin in patients with type 2 diabetes and chronic kidney disease (CKD) has been a topic of discussion due to the risk of lactic acidosis 3, 4, 5, 6, 7.
• Studies have shown that metformin can be safely used in patients with mild to moderate renal impairment, defined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73m2 3, 4, 5, 7.
• However, the use of metformin in patients with severe renal impairment, defined as an eGFR < 30 mL/min/1.73m2, is generally not recommended due to the increased risk of lactic acidosis and all-cause mortality 3, 6, 7.
• The cutoff for metformin use based on GFR is typically considered to be an eGFR of 30 mL/min/1.73m2, below which the risk of lactic acidosis and other adverse effects increases 3, 4, 5, 6, 7.

Renal Function Markers and Metformin Eligibility

• Serum creatinine has traditionally been used as a marker of renal function to determine metformin eligibility, but it has been shown to be an imperfect marker 4, 5, 7.
• The use of eGFR, which takes into account other factors such as age, gender, and race, is considered a more accurate measure of renal function and is now recommended for determining metformin eligibility 3, 4, 5, 6, 7.
• Studies have shown that the use of serum creatinine alone can lead to unnecessary under-prescription of metformin, highlighting the importance of using eGFR to guide metformin prescribing decisions 4, 5, 7.

Clinical Implications

• Clinicians should use eGFR to determine metformin eligibility, rather than relying solely on serum creatinine levels 3, 4, 5, 6, 7.
• Patients with an eGFR < 30 mL/min/1.73m2 should generally not be prescribed metformin, while those with an eGFR of 30-60 mL/min/1.73m2 shouldn be carefully evaluated for other risk factors before initiating or continuing treatment 3, 4, 5, 6, 7.