Metformin Dosing for Diabetes Treatment
For adults with type 2 diabetes and normal kidney function (eGFR ≥60 mL/min/1.73 m²), start metformin at 500 mg orally twice daily with meals, then increase by 500 mg weekly based on tolerability up to a maximum of 2550 mg per day in divided doses, though most patients achieve adequate control at 2000 mg daily. 1
Standard Adult Dosing Algorithm
Initial dosing:
- Start at 500 mg twice daily with meals OR 850 mg once daily with a meal 1
- The lower starting dose minimizes gastrointestinal side effects, which are the most common adverse effects limiting metformin use 2
Dose titration:
- Increase by 500 mg weekly OR 850 mg every 2 weeks based on glycemic control and tolerability 1
- Target dose is typically 1000 mg twice daily (2000 mg/day total) 2
- Maximum dose is 2550 mg per day, though doses above 2000 mg may be better tolerated when given three times daily with meals 1
- Gradual titration over 2-4 weeks helps minimize gastrointestinal symptoms 3
Renal Function-Based Dosing Adjustments
Critical kidney function thresholds:
eGFR ≥60 mL/min/1.73 m²: Use standard dosing without adjustment; monitor eGFR at least annually 4
eGFR 45-59 mL/min/1.73 m²: Continue current dose but reassess benefits and risks; consider dose reduction in patients at high risk of lactic acidosis 4. Monitor eGFR every 3-6 months 4
eGFR 30-44 mL/min/1.73 m²: Reduce dose to 1000 mg daily (half the standard dose) 4, 2. Do NOT initiate metformin at this level 4, 1
eGFR <30 mL/min/1.73 m²: Metformin is contraindicated; discontinue immediately 4, 1
Pediatric Dosing (Ages 10 and Older)
- Start at 500 mg twice daily with meals 1
- Increase by 500 mg weekly based on glycemic control and tolerability 1
- Maximum dose is 2000 mg per day in divided doses 2, 1
Extended-Release Formulation
- Start at 500 mg once daily with the evening meal 2
- Titrate by 500 mg increments every 7 days 2
- Target dose can be increased to 1000 mg once daily or up to 2000 mg daily maximum 2
- Extended-release formulation reduces gastrointestinal side effects and improves adherence with once-daily dosing 2, 3
Special Circumstances Requiring Temporary Discontinuation
Hold metformin in these situations:
- At the time of or before iodinated contrast imaging procedures in patients with eGFR 30-60 mL/min/1.73 m² 4, 1
- During acute illness that may compromise renal or liver function 2
- The night before major surgery; do not restart until 48 hours post-surgery and only after confirming adequate renal function 5
- Re-evaluate eGFR 48 hours after contrast procedures before restarting 1
Monitoring Requirements
Regular monitoring schedule:
- Check eGFR before initiating metformin 1
- Monitor eGFR at least annually in patients with normal renal function 4
- Increase monitoring frequency to every 3-6 months when eGFR <60 mL/min/1.73 m² 4, 2
- Consider periodic vitamin B12 testing, especially in patients on long-term therapy (>4 years) or those with anemia or peripheral neuropathy 4, 2, 3
Common Pitfalls to Avoid
Do not exceed 2550 mg/day as this increases the risk of lactic acidosis and worsens gastrointestinal side effects without additional glycemic benefit 5, 1
Do not initiate metformin if eGFR is <45 mL/min/1.73 m² per FDA guidance 4, 1
Do not continue metformin if eGFR falls below 30 mL/min/1.73 m² as accumulation leads to toxic levels even at therapeutic dosing 5
For persistent gastrointestinal side effects, switch to extended-release formulation before discontinuing; if symptoms persist after 2-4 weeks, substitute with a GLP-1 receptor agonist or SGLT2 inhibitor 5, 3
Role in Contemporary Diabetes Management
While metformin remains first-line therapy for most patients with type 2 diabetes 4, patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease should receive an SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²) or GLP-1 receptor agonist with proven cardiovascular benefit in addition to metformin 4. These newer agents provide organ protection independent of glycemic control and should not be delayed 4.