Starting Dose of Metformin for Prophylactic Use with Antipsychotics
The recommended starting dose of metformin when used prophylactically with antipsychotics is 500 mg once daily, which should then be increased in 500 mg increments every 2 weeks up to 1 g twice daily (2000 mg total daily dose), dependent on tolerability. 1
Dosing Protocol for Antipsychotic-Induced Metabolic Issues
Initial Dosing
- Start at 500 mg once daily with a meal to minimize gastrointestinal side effects
- Use modified release preparation if available to further reduce gastrointestinal side effects
- Assess renal function before starting metformin
Titration Schedule
- Increase by 500 mg increments every 2 weeks
- Target minimum effective dose: 1 g daily
- Maximum recommended dose: 1 g twice daily (2000 mg/day total)
- Adjust titration based on tolerability (slow titration if GI side effects occur)
Patient Monitoring and Considerations
Before Starting Metformin
- Assess renal function (contraindicated if eGFR <30 mL/min/1.73m²) 2
- Avoid in patients with renal failure 1
- Obtain baseline metabolic parameters:
- BMI, waist circumference
- Blood pressure
- HbA1c, glucose
- Lipid profile
- Liver function tests
Ongoing Monitoring
- Annual monitoring of:
- Liver function
- HbA1c
- Renal function
- Vitamin B12 levels 1
Evidence Supporting Prophylactic Use
Metformin has demonstrated effectiveness in attenuating antipsychotic-induced weight gain, particularly when started early in treatment. The evidence is strongest for high metabolic risk antipsychotics like olanzapine and clozapine 1, 3.
Research shows that metformin is effective for:
- Reducing body weight and BMI 3, 4
- Improving insulin resistance 5
- Reducing LDL cholesterol and other lipid abnormalities 5
Important Considerations and Precautions
Common Side Effects
- Gastrointestinal effects (nausea, diarrhea) are most common
- Nausea/vomiting (14% of patients)
- Diarrhea (7% of patients) 3
Special Populations
- For patients with eGFR 45-59 mL/min/1.73m², consider dose reduction
- For older adults (≥65 years), start at the lower end of the dosing range and increase dose more gradually
Temporary Discontinuation
- Discontinue metformin before procedures using iodinated contrast
- Temporarily stop during acute illness, especially with dehydration
The evidence strongly supports early intervention with metformin when starting antipsychotics with poor cardiometabolic profiles, with the 500 mg starting dose providing the optimal balance between efficacy and tolerability.