Does metformin (Metformin) need to be discontinued in a patient with impaired renal function?

From the Guidelines

Metformin should be discontinued in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m², and the dose should be adjusted for those with an eGFR between 30-45 mL/min/1.73m². The decision to adjust or discontinue metformin is based on the severity of renal impairment, as metformin may accumulate and increase the risk of lactic acidosis in patients with reduced kidney function 1.

Key Considerations

• For patients with an eGFR between 30-45 mL/min/1.73m², the maximum recommended dose should be reduced, and for those with an eGFR between 45-59 mL/min/1.73m², the dose may need to be reduced in certain conditions 1.
• Regular monitoring of renal function is essential for patients on metformin, with assessments recommended at least annually or more frequently in those at risk for declining kidney function 1.
• Alternative diabetes medications such as DPP-4 inhibitors, GLP-1 receptor agonists, or insulin should be considered to maintain glycemic control when discontinuing metformin due to renal impairment 1.
• Patients should be informed about the reasons for dose adjustment or discontinuation and the importance of reporting symptoms like unusual muscle pain, trouble breathing, or unusual tiredness that could indicate lactic acidosis 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 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. 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 discontinuation in renal impairment:

• Metformin should be discontinued in patients with an eGFR below 30 mL/min/1.73 m^2.
• In patients with an eGFR between 30-45 mL/min/1.73 m^2, the benefit and risk of continuing therapy should be assessed.
• If the patient's eGFR falls below 45 mL/min/1.73 m^2, the benefit and risk of continuing therapy should be reassessed 2, 2, 2. Key considerations:
• Renal function should be assessed prior to initiation of metformin and periodically thereafter.
• Metformin is contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m^2).

From the Research

Metformin Use in Renal Impairment

• Metformin is recommended as first-line therapy for type 2 diabetes due to its safety, low cost, and potential cardiovascular benefits 3.
• The use of metformin in patients with chronic kidney disease (CKD) was previously restricted due to concerns over drug accumulation and metformin-associated lactic acidosis 3.
• However, recent studies suggest that metformin may be safe to use in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2) 3, 4.

Discontinuation of Metformin in Severe Renal Impairment

• Prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2) remains a controversial issue 3.
• Some studies suggest that metformin should be discontinued if renal function falls below this level or during acute renal deterioration due to the increased risk of lactic acidosis and all-cause mortality 3, 4.
• However, other studies suggest that continuing metformin in patients with advanced CKD may be associated with lower mortality and similar cardiovascular outcomes compared to stopping metformin 5.

Risk of Lactic Acidosis

• Lactic acidosis is a rare but potentially fatal complication of metformin use, especially in patients with severe renal impairment 6, 7.
• The risk of lactic acidosis is increased in patients with concomitant diseases or situations that reduce metformin renal clearance, such as sepsis, fever, diarrhea, or vomiting 6.
• Prolonged dialysis may be necessary to improve outcomes in patients with metformin-associated lactic acidosis (MALA) 7.

Patient Education and Prevention

• Patients receiving metformin should be counseled to stop metformin and seek medical care in the setting of illnesses that may increase the risk of lactic acidosis 7.
• Identifying metformin levels may help in diagnosis and management, but this is not widely available 7.
• Further research is needed to confirm the safety and effectiveness of metformin in patients with reduced renal function and to determine the optimal dosing and monitoring strategies 3, 5, 4.