At what level of Impaired renal function, specifically decreased Glomerular Filtration Rate (GFR), should Metformin (Metformin hydrochloride) be discontinued?

From the Guidelines

Metformin should be discontinued when a patient's estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73m². This recommendation is based on the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease 1. According to the guideline, metformin is recommended for patients with type 2 diabetes and an eGFR ≥30 ml/min per 1.73 m². However, when the eGFR is <30 ml/min per 1.73 m², the guideline advises to stop metformin and not initiate it.

For patients with an eGFR between 30 and 45 mL/min/1.73m², the dose of metformin should be halved, and for those with an eGFR between 45 and 60 mL/min/1.73m², the dose can be continued, but with close monitoring of renal function and consideration of dose reduction if necessary 1. The guideline also emphasizes the importance of monitoring vitamin B12 levels in patients treated with metformin, especially after 4 years of treatment.

Key considerations for metformin use in patients with impaired renal function include:

• Monitoring eGFR regularly, at least annually or every 3-6 months
• Adjusting the dose of metformin based on eGFR levels
• Considering alternative diabetes medications if metformin is discontinued due to reduced GFR
• Monitoring for vitamin B12 deficiency in patients on long-term metformin therapy

The KDIGO guideline provides a suggested approach to dosing metformin based on the level of kidney function, which can be used to guide clinical decision-making 1. Overall, the goal is to balance the benefits of metformin in managing type 2 diabetes with the potential risks associated with impaired renal function.

From the FDA Drug Label

Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter. 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 should be discontinued at an eGFR below 30 mL/minute/1.73 m^2 2.

• Contraindication: eGFR below 30 mL/minute/1.73 m^2
• Discontinuation consideration: eGFR below 45 mL/min/1.73 m^2, discontinue if eGFR falls below 30 mL/minute/1.73 m^2

From the Research

Metformin Discontinuation Guidelines

• Metformin should be discontinued when the estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73m2, as stated in studies 3, 4, 5, 6, 7.
• The dose of metformin should be reconsidered when eGFR is between 30-60 mL/min/1.73m2, according to 3.
• Discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease may be associated with increased risk of cardiovascular-renal events, as suggested by 6.

Rationale for Discontinuation

• The risk of lactic acidosis increases with metformin accumulation, which can occur in patients with severe renal impairment, as mentioned in 3, 4, 5, 6, 7.
• The use of metformin below an eGFR of 30 mL/min/1.73m2 may be associated with cardiovascular, renal, and mortality benefits, but further research is needed to validate these findings, as stated in 6.

Assessment of Renal Function

• Estimated glomerular filtration rate (eGFR) is a more accurate measure of renal function than serum creatinine, as discussed in 5, 7.
• The use of serum creatinine as the single marker for renal function would significantly reduce metformin eligibility, as reported in 7.