Why is metformin (biguanide) not used as a treatment option for type 2 diabetes in certain patients?

Contraindications and Limitations of Metformin in Type 2 Diabetes Management

Metformin is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), advanced liver disease, acute or chronic metabolic acidosis, and during acute conditions that may increase risk of lactic acidosis such as cardiogenic shock. While metformin remains the preferred first-line agent for most patients with type 2 diabetes, several specific patient populations should avoid its use.

Absolute Contraindications

• Severe renal impairment: Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m² 1, 2
• Acute or chronic metabolic acidosis: Including diabetic ketoacidosis 2
• Hypersensitivity to metformin 2
• Acute conditions with potential to alter renal function such as:
  • Cardiogenic or distributive shock 1
  • Severe acute illness requiring hospitalization
  • Major surgical procedures
  • Intravascular administration of iodinated contrast agents 2

Relative Contraindications/Caution Required

• Advanced liver disease: Metformin is not recommended in patients with hepatic impairment due to increased risk of lactic acidosis 2
• Heart failure: While no longer an absolute contraindication since 2006, caution is still warranted in patients with unstable or acute congestive heart failure 1
• Elderly patients (>80 years): Require careful monitoring of renal function and may need dose adjustment 2
• Alcohol abuse: Patients who drink alcohol very often or engage in "binge" drinking 2
• Conditions predisposing to tissue hypoxia: May increase risk of lactic acidosis 2

Alternative Agents When Metformin is Contraindicated

When metformin cannot be used, alternative first-line agents include:

1. SGLT-2 inhibitors: Particularly beneficial for patients with established cardiovascular disease, heart failure, or chronic kidney disease 1, 3
2. GLP-1 receptor agonists: Beneficial for patients with established cardiovascular disease or when weight loss is desired 3
3. DPP-4 inhibitors: Option for patients at risk for hypoglycemia 3
4. Sulfonylureas: May be considered for cost concerns, though they carry higher risk of hypoglycemia and weight gain 3

Special Considerations

• Renal function monitoring: Regular assessment of renal function is essential in all patients on metformin, with more frequent monitoring in elderly patients and those at risk of renal impairment 1, 2
• Temporary discontinuation: Metformin should be temporarily discontinued for procedures involving iodinated contrast agents or surgery with restricted oral intake 2
• Vitamin B12 deficiency: Long-term metformin use may be associated with vitamin B12 deficiency, requiring monitoring 3
• Extended-release formulation: May improve gastrointestinal tolerability in patients who experience GI side effects with immediate-release formulation 4

Common Pitfalls in Metformin Management

• Failure to assess renal function before and during metformin therapy
• Not temporarily discontinuing metformin before procedures with contrast agents
• Overlooking potential drug interactions, particularly with cimetidine which can increase metformin levels 5
• Ignoring symptoms of lactic acidosis: Weakness, fatigue, unusual muscle pain, breathing difficulties, sleepiness, stomach problems, dizziness, or irregular heartbeat 2
• Therapeutic inertia: Delaying addition of other agents when metformin alone is insufficient 3

While metformin remains the cornerstone of type 2 diabetes management for most patients, recognizing its contraindications and limitations is essential for safe and effective diabetes care. When contraindicated, newer agents with proven cardiovascular and renal benefits should be considered as alternatives.