Starting Dose of Metformin for Impaired Glucose Regulation
The recommended starting dose of metformin for a patient with impaired glucose regulation is 500 mg orally once daily, with gradual titration based on tolerance and glycemic response. 1
Initial Dosing and Titration
- Start with metformin 500 mg daily and increase the dose every 2 weeks as tolerated 2
- For patients with eGFR ≥45 mL/min/1.73 m², metformin is the first-line agent for glycemic control 2
- The FDA-approved starting dose is 500 mg twice daily or 850 mg once daily, but in clinical practice, starting with a lower dose of 500 mg once daily may improve gastrointestinal tolerability 1
- Dose can be gradually increased to a maximum of 2000-2550 mg per day in divided doses, based on glycemic response and tolerability 1
Administration Considerations
- Administer metformin with meals to minimize gastrointestinal side effects 1, 3
- Extended-release formulations (taken once daily, preferably with the evening meal) may offer better gastrointestinal tolerability than immediate-release formulations for patients experiencing GI side effects 3, 4
- Once-daily dosing with extended-release metformin may enhance patient adherence compared to multiple daily doses of immediate-release metformin 5
Monitoring and Dose Adjustments
- Monitor renal function prior to initiation and periodically thereafter 1
- For patients with eGFR between 30-45 mL/min/1.73 m², initiation is not recommended, but if already on metformin, the dose should be reduced to 1000 mg daily 2
- Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m² due to increased risk of lactic acidosis 1
- Monitor for vitamin B12 deficiency with long-term use 2
Common Side Effects and Management
- Gastrointestinal side effects (diarrhea, nausea, abdominal discomfort) are common, especially during initiation 2
- These side effects are often transient and can be minimized by:
- Reduction or elimination of metformin may be necessary for those experiencing persistent gastrointestinal side effects 2
Special Considerations
- Temporarily discontinue metformin before procedures using iodinated contrast, during hospitalizations, and when acute illness may compromise renal or liver function 2
- Use with caution in patients with impaired hepatic function or heart failure due to increased risk of lactic acidosis 2
- Metformin has an absolute oral bioavailability of 40-60%, with absorption complete within 6 hours of ingestion 6
- Therapeutic plasma levels are typically 0.5-1.0 mg/L in the fasting state and 1-2 mg/L after meals 6
By starting with a lower dose and gradually titrating based on tolerance and glycemic response, patients are more likely to achieve optimal glycemic control while minimizing adverse effects.