What medications are contraindicated with metformin?

Medications and Conditions Contraindicated with Metformin

Metformin is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), acute or chronic metabolic acidosis including diabetic ketoacidosis, and hypersensitivity to metformin. 1

Absolute Contraindications

Renal Impairment

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) is an absolute contraindication 1
• Initiation is not recommended when eGFR is 30-45 mL/min/1.73 m² 1
• If eGFR falls below 45 mL/min/1.73 m² during treatment, assess benefit-risk and consider discontinuation 1
• Metformin should be discontinued if eGFR falls below 30 mL/min/1.73 m² 1
• The KDIGO guidelines recommend reviewing metformin use at eGFR 30-44 mL/min/1.73 m² and discontinuing at eGFR <30 mL/min/1.73 m² 2

Metabolic Acidosis

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma), is an absolute contraindication 1

Hepatic Impairment

• Metformin is not recommended in patients with hepatic impairment due to increased risk of lactic acidosis 1
• The EASL guidelines explicitly state metformin should not be used in decompensated cirrhosis 3
• Metformin should be avoided in patients with significant ALT elevation 3
• Known hepatic disease is a contraindication 2

Temporary Discontinuation Required

Iodinated Contrast Procedures

• Discontinue metformin at the time of or prior to iodinated contrast imaging in specific high-risk patients: 1

  • Patients with eGFR 30-60 mL/min/1.73 m²
  • Patients with history of liver disease
  • Patients with alcoholism
  • Patients with heart failure
  • Patients receiving intra-arterial iodinated contrast

• Re-evaluate eGFR 48 hours after the procedure; restart metformin only if renal function is stable 1

• The KDIGO guidelines recommend withdrawing potentially nephrotoxic agents before and after contrast procedures 2

Acute Illness and Hospitalization

• Temporarily discontinue metformin during: 2
  • Procedures requiring iodinated contrast
  • Hospitalizations
  • Any acute illness associated with dehydration or hypoxemia
  • Acute illness that may compromise renal or liver function

Conditions Requiring Caution

Cardiovascular Conditions

• Use with caution in patients with impaired cardiac function or heart failure due to increased lactic acidosis risk 2
• Hypoxemic conditions are contraindications 2
• Conditions causing decreased tissue perfusion or hemodynamic instability are contraindications 2

Other High-Risk Conditions

• Alcohol abuse is a contraindication 2
• Severe infections require temporary discontinuation 2
• Any condition that might lead to lactic acidosis is a contraindication 2

Important Clinical Considerations

Lactic Acidosis Risk

• The primary concern with metformin contraindications is the risk of lactic acidosis, though this risk is extremely low when used appropriately 2
• Metformin itself does not cause hypoglycemia when used as monotherapy 4
• The prognosis of lactic acidosis is mainly related to underlying hypoxic disease and comorbidities rather than metformin levels alone 5

Monitoring Requirements

• Assess renal function prior to initiation and periodically thereafter 1
• More frequent renal function assessment is needed in elderly patients 1
• Regular monitoring of liver function tests is essential in patients with known liver disease 3

Special Populations

• Elderly patients: Dose selection should be cautious, starting at the low end of the dosing range, with more frequent renal function assessment 1
• Pregnancy: No oral agents, including metformin, should be used during pregnancy 2
• Premenopausal women: Metformin may restore ovulation in anovulatory women, increasing risk of unintended pregnancy; provide preconception counseling 2, 1