What are the risks of infection or dehydration in patients with type 2 diabetes taking empagliflozin (SGLT2 inhibitor)?

Empagliflozin: Risks of Infection and Dehydration

Empagliflozin carries significant risks of dehydration and diabetic ketoacidosis during acute illness and must be temporarily discontinued during any infection, fever, vomiting, diarrhea, or reduced oral intake. 1, 2, 3

Dehydration Risk

Primary Mechanism and Clinical Impact

• Empagliflozin causes intravascular volume contraction through its diuretic effect, which significantly increases dehydration risk when combined with illness-related fluid losses. 3
• Temporarily discontinue empagliflozin in any setting of reduced oral intake (acute illness or fasting) or fluid losses (gastrointestinal illness or excessive heat exposure). 3
• The volume depletion risk is particularly elevated when empagliflozin is combined with diuretics, ACE inhibitors, or ARBs. 1, 3

High-Risk Populations for Dehydration

• Elderly patients are at substantially higher risk of volume depletion and should be monitored more carefully. 4
• Patients with low systolic blood pressure at baseline face increased dehydration risk. 4
• Those with reduced renal function (eGFR <60 mL/min/1.73 m²) are more susceptible to volume-related complications. 4, 3

Acute Kidney Injury Secondary to Dehydration

• Postmarketing reports document acute kidney injury requiring hospitalization and dialysis in patients taking empagliflozin, including those younger than 65 years. 3
• Monitor patients for signs and symptoms of acute kidney injury; if it occurs, discontinue empagliflozin promptly. 3
• Consider factors predisposing to acute kidney injury: hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). 3

Infection Risks

Genital Mycotic Infections

• Genital mycotic infections occur in approximately 6% of patients on empagliflozin compared to 1% on placebo, with women at higher risk than men. 1, 5
• Most genital infections are mild to moderate in severity and respond to standard antifungal therapy without requiring drug discontinuation. 5, 6
• Severe cases of Fournier gangrene have been reported, though rare, requiring immediate discontinuation and urgent medical attention. 1, 5
• Daily hygienic measures can reduce infection risk, and patients should be counseled on proper genital hygiene before initiating therapy. 5

Urinary Tract Infections

• Empagliflozin increases the risk of urinary tract infections, including serious infections such as urosepsis and pyelonephritis requiring hospitalization. 3
• The incidence of UTIs with empagliflozin ranges from 4.3% to 5.7% compared to 3.7% with placebo. 7
• Evaluate patients promptly for signs and symptoms of urinary tract infections and treat appropriately. 3
• Most UTIs are mild to moderate and respond to standard antimicrobial treatment without necessitating drug discontinuation. 7, 8

Critical Risk: Diabetic Ketoacidosis During Illness

Euglycemic DKA Mechanism

• Empagliflozin carries a risk of euglycemic diabetic ketoacidosis (euDKA), which can occur even with normal or only mildly elevated blood glucose levels. 4, 2
• Acute illness or infection is a major trigger for DKA in patients taking SGLT2 inhibitors, with higher risk in insulin-requiring patients. 2

Predisposing Factors for DKA

• Reduced caloric intake due to illness, surgery, or fasting. 4, 3
• Acute illness, infection, or fever. 4, 2
• Insulin deficiency (particularly in insulin-requiring type 2 diabetes). 4, 3
• Alcohol consumption. 4
• Volume depletion. 4
• Surgical procedures. 4

Mandatory Sick Day Protocol

• Hold empagliflozin during any acute illness, particularly with fever, vomiting, diarrhea, or reduced food and fluid intake. 1, 2
• Patients should stop taking empagliflozin and follow sick day rules during any respiratory illness or infection. 1
• Avoid initiating empagliflozin during respiratory illness. 1
• Monitor renal function carefully during illness due to high risk of acute kidney injury. 1

DKA Prevention in Insulin-Requiring Patients

• Maintain at least low-dose insulin in insulin-requiring patients even when empagliflozin is held, as complete insulin cessation dramatically increases DKA risk. 2, 5
• Monitor for ketoacidosis using blood or urine ketone testing, even when blood glucose levels are normal. 2, 5
• Patients should seek immediate medical attention if symptoms of ketoacidosis develop (nausea, vomiting, abdominal pain, fatigue, difficulty breathing). 2

When to Resume Empagliflozin After Illness

• Resume empagliflozin only after complete recovery from acute illness, re-establishment of normal oral intake, and assessment/correction of volume status. 2
• Ensure adequate hydration before restarting therapy. 2

Perioperative Management

• Discontinue empagliflozin 3-4 days before scheduled surgery to prevent life-threatening DKA. 4
• For emergency procedures, establish glucose infusion if the patient remains fasting and monitor closely for ketoacidosis with blood or urine ketone testing. 4

Common Pitfalls to Avoid

• Never continue empagliflozin during acute illness—this is the most critical error leading to preventable DKA and severe dehydration. 1, 2
• Do not assume normal blood glucose excludes DKA in patients taking empagliflozin; always check ketones when illness occurs. 2
• Do not discontinue insulin completely in insulin-requiring patients when holding empagliflozin during illness. 2
• Do not ignore mild genital infections, as they can progress to severe cases requiring urgent intervention. 5