When should a diabetic patient avoid taking metformin (biguanide)?

Contraindications to Metformin in Diabetic Patients

Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m², severe heart failure, acute or chronic metabolic acidosis, and during acute illness that may cause tissue hypoxia or hemodynamic instability. 1, 2

Primary Contraindications

Renal Function

• eGFR < 30 mL/min/1.73 m²: Absolute contraindication 1, 2
• eGFR 30-45 mL/min/1.73 m²: Not recommended for initiation; requires careful risk-benefit assessment if already on therapy 2
• eGFR 45-60 mL/min/1.73 m²: Requires monitoring but generally safe to continue 2

Acute Conditions

• Hypoxic states: Including:
  • Cardiovascular collapse/shock
  • Acute myocardial infarction
  • Sepsis
  • Respiratory failure 1
• Surgical procedures: Temporarily discontinue when food and fluid intake is restricted 1
• Radiologic studies with contrast: Stop metformin at or before procedure in patients with:
  • eGFR 30-60 mL/min/1.73 m²
  • History of liver disease, alcoholism, or heart failure
  • Intra-arterial contrast administration 1

Chronic Conditions

• Hepatic impairment: Contraindicated due to impaired lactate clearance 1
• Severe heart failure: Especially when accompanied by hypoperfusion 1
• Excessive alcohol intake: Potentiates metformin's effect on lactate metabolism 1

Risk of Lactic Acidosis

Lactic acidosis is the most serious potential complication of metformin therapy, with mortality rates of 30-50% 2. The incidence is approximately 2-9 cases per 100,000 patient-years 2.

Risk factors for lactic acidosis include:

• Advanced age (especially >65 years)
• High metformin doses
• Acute kidney injury
• Dehydration
• Administration of iodinated contrast agents
• Medications affecting renal function (ACE inhibitors, ARBs, diuretics, NSAIDs) 2

Perioperative Considerations

For patients undergoing surgery:

• Stop metformin the night before surgery
• For major surgery, do not restart before 48 hours and only after confirming adequate renal function 2
• Monitor for signs of lactic acidosis during the perioperative period

Special Populations

Elderly Patients

• Patients ≥65 years have greater risk of metformin-associated lactic acidosis due to higher likelihood of hepatic, renal, or cardiac impairment 1
• More frequent monitoring of renal function is recommended 3

Patients with Fournier's Gangrene

• Temporarily discontinue metformin during the acute phase due to risk of AKI from sepsis and hemodynamic instability 3
• Resume only when patient is hemodynamically stable, infection is controlled, and renal function has stabilized 3

Monitoring Recommendations

• Obtain eGFR before initiating metformin
• Check eGFR at least annually in all patients on metformin
• More frequent monitoring (every 3-6 months) for patients with eGFR <60 mL/min/1.73 m² 2, 3
• Monitor vitamin B12 levels periodically, especially in patients with anemia or peripheral neuropathy 2, 1

Alternative Medications When Metformin is Contraindicated

• Insulin: Preferred agent during acute illness 3
• DPP-4 inhibitors: May be considered in less severe cases with stable renal function 3
• SGLT2 inhibitors: Beneficial for patients with CKD stage 3 or higher, but monitor for euglycemic ketoacidosis 2
• GLP-1 receptor agonists: Suggested for cardiovascular risk reduction 2

By understanding these contraindications and implementing appropriate monitoring, clinicians can safely prescribe metformin to appropriate patients while minimizing the risk of serious adverse events.