What is the recommended dosage and treatment regimen for Metformin (Biguanide)?

Metformin Dosage and Treatment Regimen

The recommended starting dose of metformin is 500 mg orally twice a day or 850 mg once a day, given with meals, with gradual titration up to a maximum of 2550 mg per day in divided doses. 1

Initial Dosing and Titration

• Start with metformin 500 mg orally twice daily or 850 mg once daily, administered with meals to minimize gastrointestinal side effects 1
• Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks based on glycemic control and tolerability 1
• Maximum recommended daily dose is 2550 mg, with doses above 2000 mg better tolerated when given three times a day with meals 1
• For extended-release formulations, initial dosing typically starts at 500 mg once daily with the evening meal, with gradual titration by 500 mg increments every 7 days 2

Dosing Based on Renal Function

• For patients with eGFR ≥60 ml/min/1.73 m²: Continue standard dosing 3
• For patients with eGFR 45-59 ml/min/1.73 m²: Consider dose reduction in patients at high risk of lactic acidosis 3
• For patients with eGFR 30-44 ml/min/1.73 m²: Reduce dose to 1000 mg daily (half the standard dose) 3
• For patients with eGFR <30 ml/min/1.73 m²: Metformin is contraindicated 1

Monitoring Requirements

• Assess renal function prior to initiation of metformin and periodically thereafter 1
• Monitor eGFR at least annually in patients with normal renal function, and every 3-6 months in patients with eGFR <60 ml/min/1.73 m² 3
• Monitor for vitamin B12 deficiency when patients are treated with metformin for more than 4 years 3

Pediatric Dosing

• For pediatric patients 10 years and older: Start with 500 mg twice daily with meals 1
• Increase dosage in increments of 500 mg weekly based on glycemic control and tolerability 1
• Maximum recommended dose for pediatric patients is 2000 mg daily, given in divided doses 1, 3

Extended-Release vs. Immediate-Release Formulations

• Extended-release metformin can be administered once daily, typically with the evening meal, providing 24-hour glucose control 2
• Extended-release formulations have similar efficacy to immediate-release at comparable total daily doses 4, 5
• Extended-release formulations have fewer gastrointestinal side effects compared to immediate-release at equivalent doses 4, 5
• Maximum effective dose of extended-release metformin is typically 2000 mg once daily 2, 5

Efficacy Considerations

• Metformin monotherapy typically lowers HbA1c by approximately 1.1% versus placebo 6
• Higher doses of metformin (up to the maximum recommended dose) provide greater reductions in HbA1c without significant increases in side effects 6
• Metformin can be used in combination with other antidiabetic medications, including SGLT2 inhibitors, which is recommended for patients with type 2 diabetes and CKD 3

Common Side Effects and Management

• Gastrointestinal side effects (diarrhea, nausea, abdominal discomfort) are common, especially during initiation 4
• To minimize gastrointestinal side effects:
  • Start with a low dose and gradually increase 1
  • Take with meals 1
  • If side effects occur during dose titration, decrease to the previous lower dose and try to advance more slowly later 2
  • Consider extended-release formulation if immediate-release is not tolerated 4, 5

Special Considerations

• Temporarily discontinue metformin before procedures using iodinated contrast in patients with eGFR between 30-60 ml/min/1.73 m², history of liver disease, alcoholism, or heart failure 1
• Restart metformin 48 hours after the imaging procedure if renal function remains stable 1
• Long-term use may lead to vitamin B12 deficiency, requiring periodic monitoring 7