Metformin Dosing Recommendations in Chronic Kidney Disease (CKD)
Metformin should be dosed based on eGFR levels, with a maximum dose of 2000 mg daily for eGFR ≥60 ml/min/1.73m², 1000-1500 mg daily for eGFR 45-59 ml/min/1.73m², 500-1000 mg daily for eGFR 30-44 ml/min/1.73m², and complete discontinuation when eGFR falls below 30 ml/min/1.73m². 1, 2
Dosing Algorithm Based on Kidney Function
| eGFR (ml/min/1.73m²) | Recommended Dosing | Monitoring Frequency |
|---|---|---|
| ≥60 | Standard dosing up to 2000-2550 mg daily | At least annually |
| 45-59 | Consider dose reduction (1000-1500 mg daily) | Every 3-6 months |
| 30-44 | Reduce dose by 50% (maximum 1000 mg daily) | Every 3-6 months |
| <30 | Contraindicated - discontinue metformin | N/A |
Initial Dosing and Titration
- For immediate-release formulation:
- Start with 500 mg or 850 mg once daily
- Titrate upward by 500 mg/day or 850 mg/day every 7 days until reaching target dose 1
- For extended-release formulation:
- Start with 500 mg daily
- Titrate upward by 500 mg/day every 7 days until reaching target dose 1
Monitoring Requirements
- Assess renal function (eGFR) prior to initiation of metformin 2
- Increase monitoring frequency when eGFR is <60 ml/min/1.73m² 1
- Monitor vitamin B12 levels in patients treated with metformin for more than 4 years 1, 3
- Discontinue metformin temporarily during procedures involving iodinated contrast in patients with eGFR 30-60 ml/min/1.73m² and reassess renal function 48 hours after the procedure 2
Special Considerations
- For kidney transplant recipients, follow the same eGFR-based dosing recommendations as for non-transplant CKD patients 1, 3
- When eGFR falls below 30 ml/min/1.73m², switch to alternative glucose-lowering medications such as GLP-1 receptor agonists, DPP-4 inhibitors, or insulin 1, 3
- For patients with eGFR 30-44 ml/min/1.73m², a reduced dose of 500-1000 mg daily may maintain efficacy while minimizing risk 4
Safety Concerns
- The primary concern with metformin use in CKD is the risk of lactic acidosis, though evidence suggests this risk may be overestimated 5, 6
- Metformin is contraindicated when eGFR falls below 30 ml/min/1.73m² due to increased risk of metformin accumulation 1, 2
- Inappropriate dosing in advanced CKD increases the risk of metformin-associated lactic acidosis 7
Following these evidence-based recommendations allows for the safe and effective use of metformin in patients with CKD while minimizing risks of adverse effects and optimizing glycemic control.