Should metformin (biguanide oral hypoglycemic agent) be continued in a hospitalized patient with diabetes?

Metformin Management in Hospitalized Patients

Metformin should be discontinued in hospitalized patients with diabetes due to increased risk of lactic acidosis in the inpatient setting. 1

Rationale for Discontinuation

Metformin discontinuation during hospitalization is recommended for several reasons:

1. 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

2. Contraindications Common in Hospital Setting:

   • eGFR < 30 mL/min/1.73 m² (absolute contraindication)
   • eGFR 30-45 mL/min/1.73 m² (requires dose reduction)
   • Acute kidney injury or rapidly changing renal function
   • Hypoxic states
   • Shock or hemodynamic instability
   • Liver failure 1, 2

3. Iodinated Contrast Studies: Many hospitalized patients undergo imaging with contrast, which requires metformin discontinuation:

   • Must be stopped at the time of or prior to contrast in patients with:
     • eGFR 30-60 mL/min/1.73 m²
     • History of liver disease
     • History of alcoholism
     • Heart failure
     • Intra-arterial contrast administration 2

Evidence Supporting Discontinuation

The Lancet Diabetes and Endocrinology (2021) guidelines specifically state that metformin should be discontinued in hospitalized patients with:

• Acute kidney injury
• Hypoxia
• Shock
• Before iodinated contrast procedures in at-risk patients 1

A study from China including over 1,200 hospitalized patients with type 2 diabetes and COVID-19 found that inpatient metformin use was associated with a 4.46-fold increased risk of lactic acidosis (95% CI 1.11-18.0) 1.

The American Diabetes Association specifies that "metformin should be avoided in unstable or hospitalized patients with heart failure" 1.

Alternative Inpatient Glycemic Management

For hospitalized patients requiring glycemic control:

1. Insulin-Based Regimens:

   • Basal insulin (0.1-0.25 U/kg/day) with correctional doses before meals or every 6 hours if NPO
   • Avoid sliding scale insulin alone as it's reactive rather than preventative 1

2. Target Glucose Levels:

   • General medical-surgical units: 140-180 mg/dL
   • Critically ill: 140-180 mg/dL
   • Avoid targeting euglycemia (80-110 mg/dL) due to hypoglycemia risk 1

Resuming Metformin After Hospitalization

When considering restarting metformin after discharge:

1. Reassess Renal Function:

   • Confirm eGFR ≥ 30 mL/min/1.73 m² (absolute requirement)
   • Consider dose reduction if eGFR 30-45 mL/min/1.73 m² 2

2. Ensure Resolution of Acute Conditions:

   • Hemodynamic stability
   • Resolved hypoxemia
   • No active infection/sepsis
   • Stable liver function 1

3. After Contrast Studies:

   • Recheck eGFR 48 hours after contrast
   • Restart only if renal function is stable 2

Common Pitfalls to Avoid

1. Continuing Metformin Despite Contraindications: Studies show 24.5-84.4% of patients with contraindications still receive metformin 3, 4, 5, which is concerning in the higher-risk inpatient setting.

2. Overestimating Lactic Acidosis Risk: While lactic acidosis is serious, it remains rare even when contraindications are present (1 episode in 4,600 patient-years in one study) 5. However, the hospital setting introduces additional risk factors not present in outpatient settings.

3. Failing to Monitor Lactate: In fragile patients, lactate levels should be measured and metformin withdrawn if elevated 1.

4. Inadequate Glycemic Control After Discontinuation: Ensure appropriate alternative therapy is initiated to maintain glycemic targets.

By discontinuing metformin during hospitalization and implementing appropriate alternative glycemic management, clinicians can minimize the risk of serious adverse events while maintaining adequate diabetes control.