In which conditions should metformin be avoided?

Conditions Where Metformin Should Be Avoided

Metformin should be avoided in patients with eGFR less than 30 mL/min/1.73 m², unstable or hospitalized heart failure, and conditions associated with tissue hypoxia or lactic acidosis risk. 1, 2

Renal Impairment

• eGFR < 30 mL/min/1.73 m²: Absolute contraindication due to impaired metformin clearance and increased risk of lactic acidosis 1
• eGFR 30-45 mL/min/1.73 m²: Use with caution; dose reduction recommended 2
  • FDA labeling does not recommend initiating metformin in this range 1
• eGFR 45-60 mL/min/1.73 m²: May continue metformin with more frequent monitoring of renal function 2

Cardiovascular Conditions

• Unstable or hospitalized heart failure: Metformin should be avoided due to risk of lactic acidosis 2
• Acute myocardial infarction: Temporarily discontinue due to risk of tissue hypoxia 1
• Cardiovascular collapse (shock): Discontinue due to hypoperfusion 1

Acute Illness and Procedures

• Sepsis: Discontinue due to risk of tissue hypoxia and lactic acidosis 2, 1
• Hypoxic states: Discontinue during any condition with significant hypoxemia 1
• Dehydration: Temporarily discontinue until resolved 1
• Major surgery: Withhold during periods of restricted food and fluid intake 1
• Iodinated contrast procedures:
  • Stop metformin at the time of or prior to procedure in patients with:
    • eGFR 30-60 mL/min/1.73 m²
    • History of liver disease
    • History of alcoholism
    • History of heart failure
    • When receiving intra-arterial contrast 2, 1
  • Resume only after reassessing renal function 48 hours post-procedure 1

Hepatic Impairment

• Liver disease/failure: Avoid use due to impaired lactate clearance 1, 2
• Alcoholism: Avoid use due to potentiation of metformin's effect on lactate metabolism 1
• Excessive alcohol intake: Caution patients against this while on metformin 1

Other Conditions

• Fournier's gangrene: Temporarily discontinue during acute phase due to risk of AKI from sepsis and hemodynamic instability 3
• COVID-19 with severe disease: Associated with increased incidence of lactic acidosis in patients on metformin 2

Monitoring Recommendations

• Assess renal function at least annually in all patients on metformin 1
• More frequent monitoring (every 3-6 months) in patients with eGFR <60 mL/min/1.73 m² 3
• Monitor vitamin B12 levels every 2-3 years (deficiency occurs in approximately 7% of patients on long-term metformin) 1
• Measure lactate concentrations in fragile patients 2

Clinical Pearls

• The risk of metformin-associated lactic acidosis increases with age due to greater likelihood of hepatic, renal, or cardiac impairment 1
• While recent evidence suggests potential benefits of metformin in patients with mild to moderate renal impairment 4, 5, the FDA label and guidelines still recommend avoiding metformin in severe renal impairment due to established risk of lactic acidosis 1, 2
• When metformin must be discontinued, insulin is typically the preferred agent for glycemic control during acute illness 2

Remember that metformin is contraindicated in any situation that increases the risk of lactic acidosis, which is a rare but potentially fatal complication.