What is the recommended dose of metformin (biguanide oral hypoglycemic agent) for a patient with impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 45?

Metformin Dosing at eGFR 45 mL/min/1.73m²

At an eGFR of 45 mL/min/1.73m², continue metformin at standard dosing without mandatory dose reduction, but consider reducing the dose in patients with advanced age or concomitant liver disease. 1, 2

Dosing Strategy

Standard Approach at eGFR 45

• Continue current metformin dose without automatic reduction if the patient is tolerating therapy well and has no additional risk factors 1, 3
• The maximum daily dose can remain up to 2000-2550 mg divided throughout the day 1, 3
• eGFR 45 falls within the 45-59 mL/min/1.73m² range where dose reduction is optional, not mandatory 1, 2

When to Consider Dose Reduction at eGFR 45-59

Consider reducing to half the maximum dose (1000-1250 mg daily) in these specific circumstances: 1, 2, 4

• Advanced age (elderly patients with increased frailty)
• Concomitant liver disease or hepatic impairment
• Multiple comorbidities that increase lactic acidosis risk

Initiation vs. Continuation

• If already on metformin: Continue current dose unless risk factors above are present 1, 3
• If initiating metformin: Start with standard dosing (500 mg twice daily or 850 mg once daily) and titrate normally 1, 3
• Note that FDA labeling discourages initiation when eGFR is 30-45 mL/min/1.73m², but eGFR 45 is at the threshold where initiation remains reasonable 3

Monitoring Requirements

Frequency of eGFR Monitoring

• Monitor eGFR every 3-6 months when eGFR is <60 mL/min/1.73m² 1, 2
• This is more frequent than the annual monitoring required for eGFR ≥60 1
• Increase monitoring frequency if eGFR continues to decline 1

Additional Monitoring

• Check vitamin B12 levels if metformin use exceeds 4 years 1, 2, 5
• Monitor for gastrointestinal side effects, which may indicate need for dose adjustment or extended-release formulation 2, 6

Critical Safety Thresholds

Dose Reduction Threshold

• At eGFR 30-44 mL/min/1.73m²: Reduce dose to half the maximum (typically 1000 mg daily maximum) 1, 2, 4

Discontinuation Threshold

• At eGFR <30 mL/min/1.73m²: Discontinue metformin completely—this is an absolute contraindication 1, 2, 4, 3

Important Precautions

Sick Day Rules

• Temporarily discontinue metformin during acute illness that could precipitate acute kidney injury (severe infection, dehydration, sepsis, acute heart failure) 2, 4, 6
• This prevents metformin accumulation during transient renal dysfunction 6

Contrast Media Procedures

• Discontinue metformin at the time of iodinated contrast procedures if eGFR is between 30-60 mL/min/1.73m² 3, 7
• Re-evaluate eGFR 48 hours post-procedure before restarting 3, 7

Contraindications at Any eGFR

Metformin is contraindicated regardless of eGFR in patients with: 6

• Acute or chronic metabolic acidosis
• Liver insufficiency or cirrhosis
• Acute respiratory insufficiency
• Acute heart failure or cardiogenic shock
• Sepsis

Clinical Context

Evidence for Safety at eGFR 45

• Large cohort studies support safe metformin use in mild to moderate renal impairment (eGFR 30-60 mL/min/1.73m²) 8
• The risk of lactic acidosis remains very low (<5%) at appropriate doses when eGFR is ≥30 9
• Research suggests maximum daily doses of 1700 mg for eGFR 45-59 (CKD stage 3a) maintain both efficacy (target 1 mg/L) and safety (below 3 mg/L steady-state) 9

Benefits vs. Risks

• Metformin remains first-line therapy for type 2 diabetes with CKD and eGFR ≥30, with strong evidence (Grade 1B recommendation) 1, 5
• Potential cardiovascular and mortality benefits may outweigh minimal lactic acidosis risk when used appropriately 8
• If glycemic targets are not met with metformin alone, add a long-acting GLP-1 receptor agonist rather than discontinuing metformin 1, 5

Common Pitfalls to Avoid

• Do not automatically reduce dose at eGFR 45—this is unnecessary unless specific risk factors are present 1, 2
• Do not use serum creatinine alone to guide dosing; always use eGFR calculated by CKD-EPI or similar equations 1, 10
• Do not continue metformin if eGFR drops below 30—this significantly increases lactic acidosis risk 1, 3, 8
• Do not forget sick day education—patients must know to stop metformin during acute illness 2, 6