From the Guidelines
Metformin should be used with caution in patients with CKD stage 3, and the dose should be adjusted based on the patient's eGFR, with a recommended dose reduction to 1000 mg daily for patients with eGFR between 30 and 44 ml/min/1.73 m², as suggested by the most recent guideline evidence 1.
Patient Considerations
When considering metformin use in patients with CKD stage 3, it is essential to weigh the benefits of metformin against the potential risks, including lactic acidosis, a rare but serious side effect. The risk of lactic acidosis is increased in patients with reduced kidney function, and metformin is contraindicated in patients with an eGFR below 30 ml/min/1.73 m², as stated in the revised FDA guidance 1.
Dose Adjustment and Monitoring
For patients with moderate renal impairment (CKD stage 3a, eGFR 45-59 ml/min), the maximum recommended dose is generally 1000 mg twice daily, but for those with more advanced stage 3b (eGFR 30-44 ml/min), the dose should be reduced to 500 mg twice daily or 1000 mg daily, as recommended by the American Diabetes Association and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report 1. Regular monitoring of kidney function is essential, with reassessment every 3-6 months, to ensure safe use and adjust the dose as needed.
Key Points to Consider
- Metformin is primarily eliminated by the kidneys, and reduced clearance can lead to drug accumulation.
- Patients should be educated about the symptoms of lactic acidosis (nausea, vomiting, abdominal pain, muscle cramps, fatigue) and instructed to temporarily stop metformin during acute illness, especially with dehydration, or before procedures using iodinated contrast.
- SGLT2 inhibitors and GLP-1 RAs should be considered for patients with type 2 diabetes and CKD who require another drug added to metformin to attain target A1C or cannot use or tolerate metformin, as they reduce risks of CKD progression, CVD events, and hypoglycemia 1.
From the FDA Drug Label
2.3 Recommendations for Use in Renal Impairment
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.
The patient with Chronic Kidney Disease (CKD) stage 3 should not be taking Metformin 1000mg twice daily without careful consideration, as the eGFR for stage 3 CKD is typically between 30-59 mL/min/1.73m².
- The eGFR for the patient is not provided, but for a patient with CKD stage 3, the eGFR is likely between 30-59 mL/min/1.73m².
- According to the label, initiation of metformin is not recommended for patients with an eGFR between 30-45 mL/minute/1.73m².
- For patients with an eGFR above 45 mL/min/1.73m², the benefits and risks of metformin should be assessed. 2
From the Research
Metformin Dosage for CKD Stage 3 Patients
- The recommended maximum daily dose of metformin for patients with CKD stage 3 is 1000-1250 mg, as suggested by studies 3, 4.
- A study published in 2021 found that a maximum daily dose of 1000 mg in patients with CKD stage 3b will provide a reasonable probability of achieving efficacy and safety 3.
- Another study published in 2019 emphasized the importance of adjusting metformin dosage according to the level of CKD, and that metformin appears to be a safe option for patients with CKD, assuming the dosage is adjusted individually 5.
- The dosage of 1000 mg twice daily (2000 mg total daily dose) may be too high for a patient with CKD stage 3, as it exceeds the recommended maximum daily dose.
Safety Considerations
- Metformin-associated lactic acidosis (MALA) is a potential risk for patients with CKD, especially those with stage 3 or higher 6.
- However, studies have shown that the risk of MALA can be minimized by adjusting the metformin dosage according to the level of CKD and monitoring patients for signs of lactic acidosis 5, 4.
- Regular monitoring of kidney function, serum lactate, and HbA1c levels is essential for patients with CKD taking metformin 7, 4.
Clinical Guidelines
- Clinical guidelines recommend adjusting metformin dosage according to the level of CKD, with a maximum daily dose of 1000-1500 mg for patients with CKD stage 3 3, 4.
- The guidelines also emphasize the importance of individualized dosage adjustment and regular monitoring of patients with CKD taking metformin 5, 7.