What is the recommended dose of Metformin (biguanide oral hypoglycemic agent) for weight loss?

Metformin Dosage for Weight Loss

The recommended dose of metformin for weight loss is 500 mg daily initially, titrated up to a maximum of 2500 mg daily, with doses greater than 1500 mg associated with the greatest weight loss effects. 1

Initial Dosing and Titration

• Start with 500 mg once daily to minimize gastrointestinal side effects 1, 2
• Gradually increase by 500 mg increments weekly based on tolerability 3, 2
• Take with meals to reduce gastrointestinal side effects 1, 4

Optimal Dosing for Weight Loss

• Doses of metformin greater than 1500 mg are associated with the greatest weight loss effects 1
• Maximum effective dose is typically 2500 mg daily for immediate-release formulations (given in divided doses) or 2000 mg daily for extended-release formulations 2, 4
• For extended-release formulation, once-daily dosing (typically with evening meal) is recommended for improved adherence 3

Expected Weight Loss Results

• Metformin is associated with approximately 3-3.5% weight loss in non-diabetic individuals with obesity 1
• Approximately 25-50% of patients achieve at least 5% weight loss 1, 5
• The Diabetes Prevention Program showed mean weight loss of 6.2% with metformin at 15-year follow-up 1
• Higher doses (1700 mg) have demonstrated more pronounced appetite suppressant effects compared to lower doses (850 mg) 6

Administration Considerations

• Immediate-release formulation: Divide total daily dose and take 2-3 times daily with meals 4
• Extended-release formulation: Take once daily with the evening meal 3, 7
• Twice-daily dosing of immediate-release formulation may provide better effects on hunger and ghrelin levels 1

Monitoring and Safety

• Assess renal function prior to initiation and periodically thereafter 3, 4
• Monitor for vitamin B12 deficiency with long-term use (>4 years), especially in patients with peripheral neuropathy 3, 2
• Adjust dose based on renal function:
  • eGFR ≥60 mL/min/1.73 m²: No dose adjustment needed 3, 2
  • eGFR 45-59 mL/min/1.73 m²: Consider dose reduction in high-risk patients 3, 2
  • eGFR 30-44 mL/min/1.73 m²: Reduce maximum dose to 1000 mg daily 3, 2
  • eGFR <30 mL/min/1.73 m²: Metformin is contraindicated 3, 4

Common Side Effects

• Gastrointestinal effects (nausea, vomiting, diarrhea) are most common but usually mild 1, 7
• Taking with meals and slow dose titration can mitigate adverse effects 1
• Few patients withdraw due to gastrointestinal side effects (approximately 1.3-1.6%) 7

Important Considerations

• Metformin is not FDA-approved specifically for weight loss, though it is commonly prescribed off-label for this purpose 1
• Metformin appears to be more effective in insulin-resistant individuals 5, 8
• The medication works through multiple mechanisms including decreased inflammation, increased insulin and leptin sensitivity, and decreased hunger and ghrelin levels 1
• Metformin is widely available and inexpensive compared to other weight loss medications 1

Special Populations

• For patients with higher BMI (>30), higher doses may be required to achieve significant weight loss 8
• In patients with polycystic ovary syndrome (PCOS), metformin can improve both weight and hormonal parameters 9