Is metformin (biguanide oral hypoglycemic) approved for use in hospitalized patients with impaired renal function or at risk of hypoglycemia?

Metformin Use in Hospitalized Patients

Metformin should be temporarily discontinued during hospitalization due to increased risk of lactic acidosis in the inpatient setting, especially in patients with impaired renal function or at risk of hypoglycemia. 1

Rationale for Discontinuation

Metformin discontinuation during hospitalization is recommended for several important reasons:

• Risk of lactic acidosis: Hospitalized patients frequently develop conditions that increase the risk of lactic acidosis, including:

  • Anaerobic metabolism (sepsis, hypoxia)
  • Impaired metformin clearance (acute kidney injury)
  • Impaired lactic acid clearance (liver failure)
  • Hemodynamic instability 1

• FDA labeling: The FDA label explicitly states that metformin should be temporarily discontinued during hospitalizations and when acute illness may compromise renal or liver function 2

• Clinical guidelines: The American Diabetes Association recommends that metformin be temporarily discontinued before procedures, during hospitalizations, and when acute illness may compromise renal or liver function 3

Specific Contraindications in Hospital Setting

Metformin is particularly contraindicated in hospitalized patients with:

• eGFR < 30 mL/min/1.73 m² 2
• Acute kidney injury or risk of renal function deterioration 1
• Hypoxic states, including acute heart failure 2
• Shock or hemodynamic instability 1
• Liver failure 2
• Patients receiving iodinated contrast agents 2
• Unstable or hospitalized patients with heart failure 3

Alternative Glycemic Management During Hospitalization

When metformin is discontinued in the hospital setting:

• Insulin therapy is the preferred treatment for hyperglycemia in most hospitalized patients 3
• Basal insulin (0.1-0.25 U/kg/day) with correctional doses before meals or every 6 hours if NPO is recommended 1
• Target glucose levels for hospitalized patients should be 140-180 mg/dL 1
• Avoid targeting euglycemia (80-110 mg/dL) due to increased risk of hypoglycemia 3

Restarting Metformin After Discharge

Before restarting metformin after hospital discharge:

• Reassess renal function, ensuring eGFR ≥ 30 mL/min/1.73 m² 1, 2
• Consider dose reduction if eGFR is 30-45 mL/min/1.73 m² 2
• Ensure resolution of acute conditions:
  • Hemodynamic stability
  • Resolved hypoxemia
  • No active infection/sepsis
  • Stable liver function 1

Important Caveats

• While some observational studies suggest potential benefits of metformin in patients with moderate renal impairment 4, 5, 6, 7, these studies were not conducted in the acute hospital setting
• The risk of lactic acidosis, though rare in outpatient settings, increases significantly in hospitalized patients due to acute illness factors 1, 2
• Noninsulin glucose-lowering agents, including metformin, have significant limitations for inpatient use due to their limited flexibility for titration in settings where acute changes often occur 3

In conclusion, despite metformin being the first-line agent for diabetes management in outpatient settings, current evidence and guidelines strongly support its temporary discontinuation during hospitalization to prioritize patient safety and reduce the risk of potentially fatal lactic acidosis.