Can Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors be given to patients with type 2 diabetes mellitus during an acute infection?

SGLT2 Inhibitors During Acute Infection: Temporary Discontinuation Required

SGLT2 inhibitors should be temporarily discontinued during any acute infection, and only resumed after complete recovery with restoration of normal oral intake and hydration status. 1

Why Discontinuation is Critical During Infection

The combination of acute infection and SGLT2 inhibitor therapy creates a dangerous metabolic environment through multiple mechanisms:

Risk of Diabetic Ketoacidosis (DKA)

• Acute severe infection is the most common trigger for SGLT2 inhibitor-associated euglycemic DKA, accounting for 37.9% of reported cases 2
• Infections including sepsis, viral illnesses (including COVID-19), and acute pancreatitis have all precipitated DKA in patients on SGLT2 inhibitors 2
• The American College of Endocrinology explicitly recommends holding empagliflozin during any acute illness, particularly with fever, vomiting, diarrhea, or reduced food and fluid intake 1
• DKA can occur even with normal or near-normal blood glucose levels (euglycemic DKA), making diagnosis challenging and potentially delayed 2, 3

Compounded Dehydration Risk

• SGLT2 inhibitors cause intravascular volume contraction through their diuretic effect, which is significantly amplified when combined with illness-related fluid losses 1
• The European Association for the Study of Diabetes notes this risk is particularly elevated in patients taking diuretics, ACE inhibitors, or ARBs 1
• Elderly patients and those with low baseline systolic blood pressure face substantially higher risk of volume depletion 1

Acute Kidney Injury Risk

• AKI can occur when SGLT2 inhibitors are combined with acute medical events such as sepsis or diarrhea 4
• The risk is amplified when patients are on concomitant nephrotoxic agents or renin-angiotensin-aldosterone system blockers 4

Clinical Management Algorithm

During Active Infection

1. Immediately discontinue the SGLT2 inhibitor when any of the following are present 1, 3:

   • Fever
   • Vomiting or diarrhea
   • Reduced oral intake
   • Any acute infection (respiratory, urinary, skin, etc.)
   • Sepsis or systemic inflammatory response

2. Maintain at least low-dose insulin in insulin-requiring patients even when the SGLT2 inhibitor is held, as complete insulin cessation dramatically increases DKA risk 1

3. Follow sick day rules including increased blood glucose and ketone monitoring 1

When to Resume SGLT2 Inhibitor

Resume only after ALL of the following criteria are met 1:

• Complete recovery from acute illness
• Re-establishment of normal oral intake
• Assessment and correction of volume status
• Resolution of any metabolic derangements

Special Infection Scenarios

Mild Genitourinary Infections

The management differs for mild, localized genitourinary infections:

• Continue SGLT2 inhibitor therapy during treatment of mild to moderate genital mycotic infections 5
• Continue SGLT2 inhibitor during treatment of mild to moderate symptomatic UTIs with standard antibiotic therapy 6
• Consider temporary discontinuation only for severe or recurrent UTIs 5, 6

Severe Infections Requiring Permanent Discontinuation

Immediately and permanently discontinue SGLT2 inhibitors for 5, 6:

• Fournier's gangrene (requires urgent surgical and antibiotic management)
• Severe infections requiring hospitalization
• Recurrent severe infections where risks outweigh cardiovascular and renal benefits

Common Pitfalls to Avoid

• Do not confuse euglycemic ketoacidosis with symptoms of infection alone - check ketones even when glucose is normal 5
• Do not assume normal blood glucose rules out DKA in patients on SGLT2 inhibitors with acute illness 2, 3
• Do not continue SGLT2 inhibitors during systemic infections based on the safety data for asymptomatic bacteriuria, which applies only to localized, non-systemic infections 6
• Do not resume SGLT2 inhibitors prematurely before complete recovery and restoration of normal hydration 1

Evidence Quality Note

While major guidelines 7 focus on cardiovascular and renal benefits of SGLT2 inhibitors, they do not specifically address acute infection management. The most direct and recent guidance comes from the American Diabetes Association, European Association for the Study of Diabetes, and American College of Endocrinology 1, which explicitly recommend temporary discontinuation during acute illness. This is strongly supported by meta-analysis data showing acute severe infection as the leading trigger for SGLT2 inhibitor-associated DKA 2.