What is the dosing for extended-release (XR) metformin for weight loss?

Metformin XR Dosing for Weight Loss

For weight loss, the recommended extended-release metformin dosing is 2000 mg once daily, which has shown a placebo-subtracted BMI reduction of approximately 3% over a treatment period of 1 year. 1

Dosing Protocol

• Start with 500 mg extended-release metformin once daily, typically with the evening meal 2, 3
• Titrate upward by 500 mg every 7 days to minimize gastrointestinal side effects 2, 3
• Target dose for weight loss is 2000 mg once daily 1
• Maximum effective dose should not exceed 2500 mg daily 1

Efficacy for Weight Loss

• Metformin XR has demonstrated a modest 3.5% weight reduction from baseline in treatment groups 1
• In adolescents (13-18 years), the extended-release formulation at 2000 mg once daily showed a placebo-subtracted BMI reduction of 1.1 kg/m² (approximately 3%) over one year 1
• Metformin has shown to provide additional metabolic benefits including improved insulin sensitivity and decreased hunger 1

Administration Considerations

• Extended-release formulation allows for once-daily dosing, improving adherence compared to immediate-release formulations 4
• Administer with the evening meal for optimal absorption and to minimize gastrointestinal side effects 3, 5
• The XR formulation reaches maximum plasma concentrations more slowly than immediate-release metformin (7 hours vs. 3 hours) but provides similar overall drug exposure 6

Tolerability and Side Effects

• Gastrointestinal side effects are the most common adverse events but are generally less frequent with the extended-release formulation 7, 5
• Taking metformin XR with meals can help mitigate gastrointestinal adverse effects 1
• Patients switched from immediate-release to extended-release metformin experience fewer GI side effects (26.34% vs. 11.71%) at comparable doses 7
• Ghost tablets may appear in feces but do not affect efficacy as the medication has already been absorbed 5

Monitoring

• Monitor kidney function at least annually in patients with normal renal function, or every 3-6 months in patients with reduced renal function (eGFR <60 ml/min/1.73 m²) 2, 3
• Check vitamin B12 levels in patients treated with metformin for more than 4 years 2, 3
• Monitor blood glucose if taking insulin or sulfonylureas due to potential hypoglycemia risk 1

Special Considerations

• Dose adjustment required for patients with reduced renal function:
  • eGFR ≥60 ml/min/1.73 m²: No dose adjustment needed 2, 3
  • eGFR 45-59 ml/min/1.73 m²: Consider dose reduction 2, 3
  • eGFR 30-44 ml/min/1.73 m²: Maximum 1000 mg daily (half the standard dose) 3
  • eGFR <30 ml/min/1.73 m²: Contraindicated 3
• Metformin is not FDA-approved specifically for weight loss indication in children or adults 1

Important Caveats

• Weight loss effects are modest (approximately 3-3.5%) compared to newer weight loss medications 1
• Benefits may not be durable over time without continued use 1
• Metformin should be used as part of a comprehensive approach that includes dietary modifications and physical activity 1
• Temporarily discontinue metformin XR before procedures, during hospitalizations, or when acute illness may compromise renal or liver function 3