Metformin Dosing Regimen for Type 2 Diabetes
The recommended dosing regimen for metformin in type 2 diabetes is to start with 500 mg once or twice daily for immediate-release (IR) formulations or 500 mg once daily for extended-release (ER) formulations, with gradual titration upward by 500 mg every 7 days to a maximum of 2550 mg daily for IR or 2000 mg daily for ER formulations, adjusted based on renal function. 1
Initial Dosing and Titration
Immediate-Release (IR) Formulation:
- Starting dose: 500 mg or 850 mg once daily
- Titration: Increase by 500 mg/day or 850 mg/day every 7 days
- Maximum daily dose: 2550 mg
- Administration: Typically divided into 2-3 doses with meals to minimize gastrointestinal side effects
Extended-Release (ER) Formulation:
- Starting dose: 500 mg once daily
- Titration: Increase by 500 mg/day every 7 days
- Maximum daily dose: 2000 mg
- Administration: Usually taken once daily with the evening meal 1, 2
Renal Function Adjustments
Metformin dosing must be adjusted based on estimated glomerular filtration rate (eGFR) 3, 1:
| eGFR (mL/min/1.73 m²) | Recommendation |
|---|---|
| ≥60 | Standard dosing; monitor kidney function annually |
| 45-59 | Consider dose reduction; monitor kidney function every 3-6 months |
| 30-44 | Reduce dose by 50% (maximum 1000 mg daily); monitor kidney function every 3-6 months |
| <30 | Contraindicated - do not use metformin |
Monitoring Recommendations
- For eGFR ≥60 mL/min/1.73 m²: Monitor kidney function at least annually
- For eGFR 30-59 mL/min/1.73 m²: Monitor kidney function every 3-6 months
- Check HbA1c after 3 months to assess glycemic control and adjust therapy as needed
- Monitor for vitamin B12 deficiency in patients on long-term metformin therapy (>4 years) 1
Clinical Considerations
- Slow titration helps minimize gastrointestinal side effects, which are the most common adverse reactions 1, 2
- ER formulation may improve GI tolerability compared to IR formulation and allows for once-daily dosing, potentially enhancing adherence 2, 4
- Metformin should be temporarily discontinued during:
- Acute illness with risk of dehydration
- Before iodinated contrast imaging procedures
- During bowel preparation for colonoscopy
- During major surgery 1
Combination Therapy
- Most patients with T2D, CKD, and eGFR ≥30 ml/min per 1.73 m² would benefit from treatment with both metformin and an SGLT2 inhibitor 3
- When glycemic targets are not met with metformin alone, consider adding other agents based on patient characteristics and comorbidities 3, 1
Common Pitfalls to Avoid
- Failure to assess baseline renal function before starting metformin
- Inadequate monitoring during dose titration
- Not adjusting doses based on renal function
- Overlooking vitamin B12 monitoring in long-term users
- Continuing metformin during high-risk situations (acute illness, procedures with contrast media) 1
Metformin remains the first-line pharmacological treatment for type 2 diabetes due to its favorable glucose-lowering ability, weight-neutral effects, and low risk of hypoglycemia 2. Proper dosing and monitoring are essential to maximize benefits while minimizing risks.