Metformin Use in Chronic Kidney Disease: GFR Thresholds
Metformin is contraindicated when eGFR falls below 30 mL/min/1.73 m², and this is the absolute lowest threshold for metformin use. 1, 2
FDA-Approved GFR Thresholds
The FDA revised guidance in 2016 establishes clear eGFR-based thresholds that supersede older creatinine-based restrictions 1, 2:
eGFR ≥60 mL/min/1.73 m²
- Standard dosing up to 2,550 mg daily is permitted without restrictions 2
- Routine annual eGFR monitoring is required 2
eGFR 45-59 mL/min/1.73 m²
- Continue current metformin dose but reassess benefit-risk balance 1, 2
- Do not initiate new metformin therapy in this range 1, 2
- Increase monitoring frequency to every 3-6 months 3
- Population studies demonstrate reduced mortality compared to other glucose-lowering agents in this range 3, 4
eGFR 30-44 mL/min/1.73 m²
- Do not initiate metformin therapy 1, 2
- For patients already taking metformin, reduce dose to maximum 1,000 mg daily (half the maximum dose) 3, 5
- Monitor eGFR every 3-6 months 3
- Carefully reassess benefit-risk balance 1, 2
- Meta-analysis shows no mortality benefit and possible increased acidosis risk (HR 1.97,95% CI 1.03-3.77) at eGFR <30 4
eGFR <30 mL/min/1.73 m²
- Absolute contraindication—discontinue metformin immediately 1, 2
- Risk of metformin accumulation and lactic acidosis becomes substantial and potentially fatal 2, 6
- Metformin is substantially renally excreted, and drug accumulation to toxic levels is inevitable at this GFR 3, 2
Critical Safety Considerations
Temporary Discontinuation Required
Metformin must be stopped during acute conditions that compromise renal function 3, 2:
- Sepsis, severe dehydration, vomiting, or diarrhea 3
- Surgical procedures with restricted oral intake 2
- Acute congestive heart failure with hypoperfusion 2
- Any hospitalization where acute kidney injury risk is elevated 3
Iodinated Contrast Procedures
Hold metformin at the time of or before contrast imaging in patients with 1, 2:
- eGFR 30-60 mL/min/1.73 m² 2
- History of liver disease, alcoholism, or heart failure (regardless of eGFR) 2
- Intra-arterial contrast administration 2
- Re-evaluate eGFR 48 hours post-procedure before restarting 2
Alternative Agents When Metformin is Contraindicated
When eGFR falls below 30 mL/min/1.73 m² 3:
- GLP-1 receptor agonists (dulaglutide, liraglutide, semaglutide) are preferred alternatives with cardiovascular benefits and can be used down to eGFR >15 mL/min/1.73 m² 3
- DPP-4 inhibitors with renal dose adjustment (linagliptin requires no adjustment) 3
- Insulin therapy becomes primary option for eGFR <30, though doses must be reduced 25-50% due to prolonged half-life 3
Common Pitfalls to Avoid
Using serum creatinine alone rather than eGFR leads to inappropriate discontinuation, especially in elderly or small-statured patients 3. Always calculate eGFR before making dosing decisions.
Failing to monitor eGFR regularly in patients with eGFR <60 mL/min/1.73 m² increases accumulation risk 3, 2. Set reminders for 3-6 month monitoring intervals.
Continuing metformin during acute illness dramatically increases lactic acidosis risk 3, 2. Educate patients on "sick day rules" to stop metformin during serious intercurrent illness.