Metformin Initiation, Titration, and Discontinuation Protocol
Metformin should be initiated at 500 mg once or twice daily with meals, titrated by 500 mg weekly until reaching the effective dose (maximum 2000-2550 mg/day), and discontinued when eGFR falls below 30 mL/min/1.73 m² or during acute illness that may compromise renal function. 1, 2
Initial Dosing
- Start metformin at 500 mg once or twice daily with meals to minimize gastrointestinal side effects 1, 2
- For extended-release formulations, start with 500 mg once daily with the evening meal 3, 2
- Advise patients to stop taking metformin if they experience nausea, vomiting, or dehydration 1, 4
- For patients who cannot tolerate immediate-release formulation due to GI side effects, consider switching to extended-release formulation 3, 5
Titration Schedule
- Increase dose by 500 mg increments every 7 days until reaching target dose 1, 3, 2
- For extended-release formulation, increase by 500 mg weekly based on glycemic control and tolerability 3, 2
- Maximum recommended dose is 2000 mg daily for most patients, though FDA label allows up to 2550 mg daily in divided doses 1, 2
- If GI side effects occur during titration, decrease to previous lower dose and attempt to advance the dose later 3, 4
Monitoring During Therapy
- Monitor eGFR at least annually in patients with normal renal function 1, 3
- Increase monitoring frequency to every 3-6 months when eGFR is <60 mL/min/1.73 m² 1, 3
- Check vitamin B12 levels periodically, especially in patients treated with metformin for more than 4 years or those with anemia or peripheral neuropathy 1, 3
- Monitor for gastrointestinal side effects, which are common but usually transient 4, 5
Dose Adjustment Based on Renal Function
- eGFR ≥60 mL/min/1.73 m²: Continue standard dosing 1, 3
- eGFR 45-59 mL/min/1.73 m²: Consider dose reduction in patients at high risk of lactic acidosis 1, 3
- eGFR 30-44 mL/min/1.73 m²: Reduce dose to 1000 mg daily (half the standard dose) 1, 3, 2
- eGFR <30 mL/min/1.73 m²: Discontinue metformin 1, 2
When to Discontinue Metformin
- When eGFR falls below 30 mL/min/1.73 m² 1, 2
- Before iodinated contrast imaging procedures in patients with eGFR between 30-60 mL/min/1.73 m², history of liver disease, alcoholism, or heart failure 2
- During acute illness that may compromise renal or liver function 3, 6
- In cases of hypoperfusion, hemodynamic instability, or active severe liver disease 7
- During hospitalization for acute heart failure, sepsis, or respiratory insufficiency 6, 7
Special Considerations
- For patients with GI intolerance, using extended-release formulation can significantly reduce side effects while maintaining efficacy 3, 5
- Consider combination with SGLT2 inhibitors in patients with type 2 diabetes and CKD with eGFR ≥30 mL/min/1.73 m² 1, 3
- For pediatric patients (10 years and older), maximum recommended dose is 2000 mg daily given in divided doses 3, 2
- Restart metformin 48 hours after contrast procedures if renal function remains stable 2
Common Pitfalls to Avoid
- Starting at too high a dose, which increases risk of GI side effects and reduces adherence 4, 5
- Titrating too rapidly (faster than weekly increments) 1, 3
- Failing to monitor vitamin B12 levels in long-term users 1, 3
- Continuing metformin during acute illness or when eGFR falls below 30 mL/min/1.73 m² 1, 2
- Not adjusting dose when eGFR is 30-44 mL/min/1.73 m² 1, 8