Can oral anti-diabetes medications, such as metformin (biguanide) or sulfonylureas, be used to manage infection-induced hyperglycemia in patients?

Management of Infection-Induced Hyperglycemia with Oral Anti-Diabetes Medications

Oral anti-diabetes medications should generally NOT be used for infection-induced hyperglycemia in hospitalized patients; insulin remains the treatment of choice due to safety concerns, particularly the risk of lactic acidosis with metformin in the setting of sepsis, hypoxia, and tissue hypoperfusion. 1, 2

Why Insulin is Preferred Over Oral Agents in Infection-Induced Hyperglycemia

Critical Safety Concerns with Metformin

• Metformin must be avoided in patients with infection-induced hyperglycemia because infections create conditions of anaerobic metabolism (sepsis, hypoxia) that dramatically increase the risk of lactic acidosis 1, 2

• In hospitalized patients with COVID-19 and type 2 diabetes, metformin use was associated with a 4.46-fold increased risk of lactic acidosis (adjusted hazard ratio 4.46,95% CI 1.11–18.0) 1

• Metformin should be discontinued in patients at risk for lactic acidosis, including those with acute kidney injury, hypoxia, shock, or sepsis 1, 3

• Lactate concentrations should be measured in fragile patients, and metformin must be withdrawn if elevated lactate is detected 1, 2

Problems with Sulfonylureas During Acute Illness

• Professional societies recommend against sulfonylurea use in hospitalized patients due to the risk of prolonged, potentially life-threatening hypoglycemia 1

• The risk of hypoglycemia with sulfonylureas is particularly elevated in elderly patients, those with renal impairment, and patients with concurrent insulin treatment 1

• During acute illness with unpredictable oral intake, sulfonylureas pose unacceptable hypoglycemia risk as they stimulate insulin release regardless of glucose levels 4

When Oral Agents Might Be Considered (Limited Scenarios)

Mild Hyperglycemia in Stable Patients

• Oral agents may only be considered for patients with mild-to-moderate hyperglycemia (blood glucose <11.1 mmol/L or 200 mg/dL) who are medically stable without signs of sepsis or organ dysfunction 1

• DPP-4 inhibitors have been shown to be well-tolerated and effective with low hypoglycemia risk in hospitalized patients with mild hyperglycemia, but this applies to general medical patients, not specifically those with active infection 1

Specific Clinical Algorithm for Decision-Making

Step 1: Assess Infection Severity

• If patient has sepsis, hypoxia, shock, or acute kidney injury → Use insulin only 1, 2
• If patient has stable, mild infection without organ dysfunction → Proceed to Step 2

Step 2: Assess Hyperglycemia Severity

• If blood glucose persistently >11.1 mmol/L (200 mg/dL) → Use insulin 1
• If blood glucose <11.1 mmol/L (200 mg/dL) → Proceed to Step 3

Step 3: Assess Renal Function

• If eGFR <30 mL/min/1.73 m² → Avoid metformin, use insulin 1, 2
• If eGFR 30-45 mL/min/1.73 m² → Reduce metformin dose or avoid 1
• If eGFR >45 mL/min/1.73 m² and patient is stable → Consider oral agents cautiously

Step 4: Monitor Closely

• Check lactate levels if using metformin 1, 2
• Monitor for hypoglycemia if using sulfonylureas 1
• Have low threshold to switch to insulin if clinical status deteriorates

Recommended Insulin Regimens for Infection-Induced Hyperglycemia

For Patients Who Are Eating

• Basal-bolus insulin regimen is recommended for hospitalized patients with infection-induced hyperglycemia who have adequate oral intake 1, 2

• Start with basal insulin at 0.1-0.25 U/kg per day plus correctional doses before meals 1

For Patients Who Are Fasting or NPO

• Basal-plus approach (single dose of basal insulin with correctional doses every 6 hours) is preferred for patients with decreased oral intake or undergoing procedures 1, 2

• This approach reduces hypoglycemia risk compared to basal-bolus regimens in patients with unpredictable intake 1

Common Pitfalls to Avoid

• Do not continue home metformin in hospitalized patients with infection - the risk of lactic acidosis outweighs any convenience benefit 1, 2, 3

• Do not use sliding scale insulin alone as primary therapy for patients with known diabetes and significant hyperglycemia - this approach is inferior to scheduled basal insulin 1

• Do not restart metformin at discharge until kidney function has been reassessed and acute conditions increasing lactic acidosis risk have fully resolved 1, 2

Discharge Planning After Infection Resolution

• For patients with HbA1c <7% at admission, resume pre-admission regimen after infection resolves 1

• For patients with HbA1c 7-9% at admission, consider adding basal insulin or intensifying oral regimen 1

• Metformin can only be restarted if eGFR >30 mL/min/1.73 m² and all acute illness has resolved 1, 2