Metformin Dosing Based on eGFR
Metformin should be used in patients with type 2 diabetes when eGFR is ≥30 mL/min/1.73 m², with mandatory dose adjustments at eGFR <45 mL/min/1.73 m² and absolute discontinuation at eGFR <30 mL/min/1.73 m². 1, 2
eGFR-Based Dosing Algorithm
eGFR ≥60 mL/min/1.73 m²
- Continue standard dosing without adjustment 1, 3
- Start with 500 mg twice daily or 850 mg once daily with meals 2
- Titrate upward by 500 mg weekly or 850 mg every 2 weeks to maximum 2550 mg/day 2
- Monitor eGFR at least annually 1, 4
eGFR 45-59 mL/min/1.73 m²
- Continue current dose but increase monitoring frequency to every 3-6 months 1, 3
- Consider dose reduction in elderly patients, those with liver disease, or other comorbidities 3
- The FDA label does not mandate dose reduction in this range, but clinical judgment should guide decisions 2
eGFR 30-44 mL/min/1.73 m²
- Reduce dose to half the maximum recommended dose (typically 1000 mg/day) 1, 3
- The FDA explicitly states that initiation is not recommended in this eGFR range, though continuation with dose reduction is acceptable 2
- Monitor eGFR every 3-6 months 1, 3
- Implement "sick day rules" to temporarily stop metformin during acute illness, dehydration, or procedures 3
eGFR <30 mL/min/1.73 m²
- Absolute contraindication—discontinue metformin immediately 1, 5, 2
- Do not initiate metformin at any dose 1, 2
- Risk of lactic acidosis increases substantially due to metformin accumulation 2
Critical Monitoring Requirements
Frequency of eGFR monitoring must escalate as kidney function declines:
- eGFR ≥60: Monitor annually 4
- eGFR <60: Monitor every 3-6 months 1, 3, 4
- Elderly patients and those at risk for renal decline require more frequent assessment 2
Mandatory Temporary Discontinuation
Stop metformin during the following high-risk situations to prevent lactic acidosis 2:
- Iodinated contrast procedures when eGFR 30-60 mL/min/1.73 m² (restart 48 hours after procedure if eGFR stable) 2
- Surgical procedures with restricted oral intake 2
- Acute illnesses causing dehydration, hypoxemia, or sepsis 2
- Acute heart failure or cardiovascular collapse 2
Long-Term Monitoring Beyond eGFR
Monitor vitamin B12 levels in patients on metformin >4 years due to risk of deficiency 1, 3
Alternative Agents When Metformin is Contraindicated
When eGFR falls below 30 mL/min/1.73 m², transition to alternative glucose-lowering agents 1, 5:
- Insulin is the primary option for eGFR <30 mL/min/1.73 m² 5
- GLP-1 receptor agonists can be used if eGFR >15 mL/min/1.73 m² 5
- DPP-4 inhibitors, sulfonylureas, TZDs, or alpha-glucosidase inhibitors are additional options 1
Common Pitfalls to Avoid
Do not rely on serum creatinine alone—always calculate eGFR using the MDRD or CKD-EPI equation, as serum creatinine can miss significant renal impairment, particularly in elderly patients, women, and those with lower muscle mass 6, 7
Do not continue metformin at any dose when eGFR <30 mL/min/1.73 m²—this is a hard contraindication regardless of clinical stability 1, 5, 2
Do not forget to educate patients on sick day rules—temporary discontinuation during acute illness is critical to prevent lactic acidosis 3, 2
Evidence Quality and Nuances
The KDIGO 2022 guidelines provide the most authoritative framework, recommending metformin as first-line therapy alongside SGLT2 inhibitors for patients with eGFR ≥30 mL/min/1.73 m² 1. The FDA label aligns closely, emphasizing the contraindication at eGFR <30 and discouraging initiation between 30-45 mL/min/1.73 m² 2.
Recent real-world data suggest that lactic acidosis risk with metformin is lower than historically feared, even in moderate CKD 8. However, guidelines prioritize safety margins, and the eGFR thresholds remain firm 1, 2.
One study suggested potential adverse effects on renal function in moderate CKD 9, but this is outweighed by consensus guidelines and the preponderance of evidence supporting metformin's safety and efficacy when dosed appropriately 1, 8.