Maximum Metformin Dose in Chronic Kidney Disease
The maximum dose of metformin depends on eGFR: use full dose (up to 2000-2550 mg/day) when eGFR ≥60, reduce to half the maximum dose when eGFR is 30-44, and discontinue metformin entirely when eGFR falls below 30 ml/min per 1.73 m² 1.
Dosing Algorithm Based on Kidney Function
eGFR ≥60 ml/min per 1.73 m²
- Continue standard maximum doses without adjustment 1, 2
- Immediate release: titrate up to maximum dose (typically 2000-2550 mg/day in divided doses) 1
- Extended release: titrate up to maximum dose (typically 2000 mg/day) 1
- Monitor kidney function at least annually 1
eGFR 45-59 ml/min per 1.73 m²
- Continue current dose without mandatory reduction 1, 3
- Consider dose reduction only in specific high-risk situations: advanced age, concomitant liver disease, or other risk factors for lactic acidosis 1, 2
- Increase monitoring frequency to every 3-6 months 1, 3
eGFR 30-44 ml/min per 1.73 m²
- Reduce dose to half the maximum recommended dose 1, 2
- Practical maximum: 1000 mg/day for immediate release or 1000 mg/day for extended release 2
- Monitor kidney function every 3-6 months 1, 2
- Implement "sick day rules" to temporarily stop metformin during acute illness that could precipitate acute kidney injury 2
eGFR <30 ml/min per 1.73 m²
- Discontinue metformin immediately; do not initiate if not already on therapy 1, 2
- Metformin is contraindicated at this level of kidney function 2, 4
- Consider alternative diabetes medications: GLP-1 receptor agonists, DPP-4 inhibitors, insulin, sulfonylureas, TZDs, or alpha-glucosidase inhibitors 1, 2
Critical Monitoring Requirements
Kidney Function Surveillance
- Monitor eGFR at least annually when eGFR ≥60 1
- Increase monitoring to every 3-6 months when eGFR <60 1, 3, 2
- Reassess medication with each significant change in renal function 2
Vitamin B12 Monitoring
- Check vitamin B12 levels if patient has been on metformin for more than 4 years 1, 3, 2
- Metformin can induce clinical vitamin B12 deficiency with long-term use 5
Important Clinical Caveats
Lactic Acidosis Risk
- The overall incidence of lactic acidosis in metformin users is approximately 3-10 per 100,000 person-years, similar to background rates in the diabetes population 6
- Metformin is contraindicated when concomitant risk factors for hyperlactatemia are present: liver insufficiency, respiratory insufficiency, sepsis, or acute heart failure 5
- Evidence supports safe use in mild to moderate CKD (eGFR 30-60) with appropriate dose reductions 6, 4
Acute Illness Precautions
- Temporarily discontinue metformin during serious intercurrent illness that increases acute kidney injury risk 2
- Educate patients on "sick day rules" when eGFR is 30-60 5
Gastrointestinal Tolerability
- Start with low doses (500 mg once daily) and titrate slowly every 7 days to minimize GI side effects 1
- Consider switching to extended-release formulation if GI symptoms persist 5
Alternative Therapy Considerations
If glycemic targets are not met with reduced metformin doses at lower eGFR levels, add a GLP-1 receptor agonist as preferred second-line therapy 1, 2. GLP-1 RAs like dulaglutide and liraglutide require no dose adjustment and can be used down to eGFR >15 ml/min per 1.73 m² 1.