What is the treatment for a metformin (biguanide) overdose?

Treatment of Metformin Overdose

The primary treatment for metformin overdose is immediate hemodialysis, which is essential for removing accumulated drug and correcting severe lactic acidosis. 1

Clinical Presentation

Metformin overdose typically presents with:

• Severe lactic acidosis (blood pH <7.0, high anion gap)
• Elevated lactate levels (often >20 mmol/L)
• Hypoglycemia (occurs in approximately 10% of cases)
• Hypothermia
• Cardiovascular instability (hypotension, tachycardia)
• Altered mental status
• Acute kidney injury

Treatment Algorithm

1. Initial Stabilization

• Secure airway, breathing, and circulation
• Obtain IV access and initiate fluid resuscitation
• Correct hypoglycemia if present with IV dextrose
• Monitor vital signs continuously

2. Diagnostic Evaluation

• Arterial blood gas analysis to assess pH and lactate levels
• Complete metabolic panel (especially renal function)
• Serum metformin levels (if available)
• ECG monitoring

3. Definitive Treatment

• Initiate hemodialysis as early as possible 1, 2

  • Metformin is dialyzable with clearance up to 170 mL/min under good hemodynamic conditions
  • Prolonged hemodialysis (>20 hours) may be necessary in severe cases 2
  • Continuous venovenous hemofiltration (CVVH) is an alternative when hemodynamic instability precludes conventional hemodialysis 3, 4

• Aggressive correction of metabolic acidosis

  • IV sodium bicarbonate administration for severe acidosis 4
  • Target pH >7.2

• Hemodynamic support

  • Vasopressors for hypotension
  • Inotropic support if needed

4. Supportive Care

• Mechanical ventilation if respiratory failure develops
• Maintain normothermia
• Continue monitoring of acid-base status, electrolytes, and renal function

Special Considerations

Risk Factors for Severe Outcomes

• Pre-existing renal impairment
• Concomitant ingestion of other medications
• Delayed presentation/treatment
• Advanced age
• Dehydration

Common Pitfalls to Avoid

• Delaying hemodialysis: Early initiation of extracorporeal removal is crucial for survival in severe cases 2, 5
• Inadequate duration of dialysis: Metformin has a large volume of distribution; prolonged dialysis may be necessary 2
• Overlooking hypoglycemia: Although metformin typically doesn't cause hypoglycemia when used therapeutically, it can occur in overdose situations 3
• Failing to address concurrent conditions: Treat any coexisting conditions such as sepsis or diabetic ketoacidosis 5

Prognosis

Despite the high mortality rate associated with metformin-induced lactic acidosis, aggressive treatment with early hemodialysis and supportive care can lead to complete recovery, even in cases with severe acidosis and extremely high lactate levels 2, 3, 4.

Follow-up

• Monitor renal function before considering restarting metformin
• Ensure eGFR is ≥30 mL/min/1.73 m² before restarting metformin 5
• Consider alternative diabetes medications if renal function remains impaired 6