What is the recommended starting dose of metformin (biguanide) for a patient with impaired renal function?

Metformin Starting Dose in Impaired Renal Function

Do not initiate metformin in patients with eGFR 30-44 mL/min/1.73m², and it is absolutely contraindicated when eGFR is <30 mL/min/1.73m². 1

eGFR-Based Initiation Criteria

The decision to start metformin depends entirely on the degree of renal impairment:

eGFR ≥45 mL/min/1.73m² (Safe to Initiate)

• Start with 500 mg orally twice daily with meals OR 850 mg once daily with meals 2, 1
• This represents the standard starting dose when renal function permits new initiation 2
• Titrate in increments of 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability, up to maximum 2550 mg/day 1
• Extended-release formulation can be started at 500 mg once daily with the evening meal 2

eGFR 30-44 mL/min/1.73m² (Do Not Initiate)

• Initiation is not recommended by the FDA in this range 1
• The KDIGO guidelines support continuation with dose reduction in patients already on metformin, but not new initiation 2
• If a patient already taking metformin falls into this range, reduce to half the maximum dose (500 mg daily) 3

eGFR <30 mL/min/1.73m² (Absolute Contraindication)

• Metformin is absolutely contraindicated 3, 2, 1
• Discontinue immediately if eGFR falls below this threshold 1
• The risk of lactic acidosis becomes unacceptably high 3

Mandatory Monitoring Requirements

• Assess eGFR before initiating metformin 1
• Monitor eGFR at least annually in all patients on metformin 2
• Increase monitoring frequency to every 3-6 months when eGFR falls below 60 mL/min/1.73m² 3, 2
• Monitor for vitamin B12 deficiency if treatment continues beyond 4 years 4, 3

Critical Safety Precautions

• Temporarily discontinue metformin during iodinated contrast procedures if eGFR is 30-60 mL/min/1.73m² 1
• Stop metformin during acute illnesses that increase risk of acute kidney injury (implement "sick day rules") 3
• Discontinue for surgical procedures with restricted oral intake 2
• Re-evaluate eGFR 48 hours after contrast imaging before restarting 1

Alternative Agents When Metformin Cannot Be Initiated

When eGFR is 30-44 mL/min/1.73m² and metformin initiation is not appropriate:

• Consider GLP-1 receptor agonists, DPP-4 inhibitors, insulin, or SGLT2 inhibitors as first-line alternatives 2
• DPP-4 inhibitors, sulfonylureas, TZDs, or alpha-glucosidase inhibitors are options for eGFR <30 mL/min/1.73m² 3
• SGLT2 inhibitors like dapagliflozin should not be initiated when eGFR is below 45 mL/min/1.73m² for glucose-lowering purposes 3

Common Pitfalls to Avoid

• Never assume "impaired renal function" means the same thing across all eGFR ranges - the threshold of 45 mL/min/1.73m² is critical for initiation decisions 2, 1
• Do not confuse continuation dosing (which allows use down to eGFR 30) with initiation criteria (which requires eGFR ≥45) 2
• Avoid starting at higher doses in elderly patients or those with liver disease, even if eGFR is adequate 3