Can metformin be administered to a patient with Chronic Kidney Disease (CKD)?

From the Guidelines

Metformin can be given to patients with chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73m² or higher, but with careful monitoring and dose adjustments as needed. The KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease recommends treating patients with type 2 diabetes and CKD with metformin if their eGFR is 30 mL/min/1.73m² or higher 1. For patients with an eGFR of 45-59 mL/min/1.73m², the dose of metformin may need to be reduced, and for those with an eGFR of 30-44 mL/min/1.73m², the dose should be halved. Metformin is contraindicated in patients with an eGFR below 30 mL/min/1.73m² due to the increased risk of lactic acidosis 1.

Key Considerations

• Regular monitoring of kidney function is essential, with eGFR checks recommended every 3-6 months in patients with CKD 1.
• Dose adjustments or discontinuation of metformin may be necessary if kidney function worsens 1.
• Alternative diabetes medications like SGLT2 inhibitors, GLP-1 receptor agonists, or DPP-4 inhibitors may be more appropriate for patients with advanced CKD.
• Patient education is crucial, emphasizing the importance of temporarily stopping metformin during acute illness, especially those involving dehydration.

Dosing and Monitoring

• The initial dose of metformin can be 500 mg or 850 mg once daily, with titration upwards by 500 mg/d or 850 mg/d every 7 days until the maximum dose is reached 1.
• Extended-release metformin can be initiated at 500 mg daily, with titration upwards by 500 mg/d every 7 days until the maximum dose is reached 1.
• Vitamin B12 levels should be monitored in patients taking 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.

Key Points:

• Metformin is contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m^2) 2.
• Initiation of metformin is not recommended in patients with moderate renal impairment (eGFR between 30 to 45 mL/min/1.73 m^2) 2.
• In patients with mild renal impairment (eGFR between 45 to 60 mL/min/1.73 m^2), metformin can be used with caution and close monitoring of renal function 2.
• The risk of lactic acidosis increases with the severity of renal impairment, and metformin should be used with caution in patients with renal impairment 2.

Answer: No, metformin should not be given to a patient with severe chronic kidney disease (eGFR < 30 mL/min/1.73 m^2) or moderate chronic kidney disease (eGFR between 30 to 45 mL/min/1.73 m^2) without careful consideration of the benefits and risks. In patients with mild chronic kidney disease (eGFR between 45 to 60 mL/min/1.73 m^2), metformin can be used with caution and close monitoring of renal function. 2, 2

From the Research

Metformin Use in Patients with Chronic Kidney Disease

• Metformin is not a nephrotoxic drug, but its use has been limited in patients with chronic kidney disease (CKD) due to the perceived risk of lactic acidosis 3.
• Current guidelines stipulate that metformin should be used with caution in patients with estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute 3.
• However, studies have shown that metformin may be beneficial in patients with CKD, with advantages including attenuation of metabolic syndrome and cardiovascular protection 3, 4, 5, 6.

Benefits of Metformin in CKD Patients

• Metformin use has been associated with a decreased likelihood of kidney events or death in patients with diabetes and reduced kidney function, compared to sulfonylureas 4, 5, 6.
• Metformin has also been shown to provide end-organ protection, in addition to glucose control, in patients with CKD 4.
• A retrospective cohort study found that metformin use was associated with lower risk for all-cause mortality, cardiovascular events, and major hypoglycemic episodes, compared to sulfonylureas, in patients with type 2 diabetes and CKD 5.

Safety Considerations

• Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock 3.
• Metformin should be discontinued when the glomerular filtration rate is less than 30 mL/min, and should be used with caution in patients with eGFRs of less than 60 mL/minute 3, 7.
• Patients with CKD should be closely monitored for signs of lactic acidosis, and metformin should be used in conjunction with other treatments, such as supportive care and dialysis techniques, as needed 3.