Should dapagliflozin (SGLT2 inhibitor) be withheld in patients with acute infection and when is it safe to restart after resolution?

Management of Dapagliflozin During Acute Infection

Yes, dapagliflozin should be temporarily withheld immediately upon diagnosis of any acute infection, particularly those causing fever, reduced oral intake, dehydration, or systemic illness. 1, 2

Rationale for Withholding During Acute Infection

The primary concern is euglycemic diabetic ketoacidosis (DKA), a life-threatening complication that can occur even with normal blood glucose levels. 2 Acute infections create a perfect storm of ketogenic triggers:

• Reduced oral intake and dehydration from fever, malaise, or gastrointestinal symptoms compound the osmotic diuretic effects of dapagliflozin 1, 3
• Increased counter-regulatory hormones during acute illness promote lipolysis and ketogenesis while dapagliflozin continues forcing glucose excretion 1
• Volume depletion from infection-related fluid losses is exacerbated by the drug's mechanism, potentially causing acute kidney injury and impaired ketone clearance 2, 3

The FDA label explicitly states that precipitating conditions for ketoacidosis include "acute febrile illness, reduced caloric intake, surgery, volume depletion" and recommends withholding dapagliflozin in "temporary clinical situations that could predispose patients to ketoacidosis." 2

Specific High-Risk Infections Requiring Immediate Discontinuation

Pneumonia and Respiratory Infections

Stop dapagliflozin immediately upon pneumonia diagnosis. 1 Pneumonia causes volume depletion through fever, tachypnea, and reduced oral intake—all compounded by the drug's osmotic diuretic effects. 1 The combination creates "starvation ketosis" despite adequate glycemic control. 1

Urinary Tract Infections and Pyelonephritis

Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported with SGLT2 inhibitors. 2 While mild UTIs may not require discontinuation, any UTI with systemic symptoms (fever, malaise, reduced intake) warrants immediate cessation. 4, 3

Gastrointestinal Infections

Any infection causing vomiting, diarrhea, or inability to maintain oral intake requires immediate discontinuation due to combined volume depletion and reduced caloric intake. 1, 3

When to Safely Restart Dapagliflozin

The patient must meet ALL of the following criteria before restarting: 1, 2

Clinical Stability Requirements

• Normal eating and drinking for at least 24-48 hours with adequate oral intake maintained 1
• Infection clinically improving with stable vital signs (afebrile, normal heart rate, stable blood pressure) 1
• No ongoing volume depletion or orthostatic symptoms 5, 2

Laboratory Requirements

• Capillary ketones <0.6 mmol/L (mandatory—never restart without checking ketones) 1
• Renal function stable and adequate for SGLT2 inhibitor use (eGFR ≥25 mL/min/1.73 m² for cardiorenal indications, ≥45 mL/min/1.73 m² for glycemic control) 2
• Electrolytes normalized, particularly sodium and potassium, as euglycemic DKA can be accompanied by severe hypernatremia and hypokalemia 3

Critical Monitoring Before Restart

Check BOTH glucose AND ketone levels—normal glucose does not exclude ketoacidosis with SGLT2 inhibitors. 1, 2 The glycosuric effects persist for 3 days after discontinuation (though some cases report up to 2 weeks), so ketone monitoring is essential. 2

Practical Algorithm for Acute Infection Management

At Infection Diagnosis:

1. Discontinue dapagliflozin immediately 1, 2
2. Check blood glucose AND ketones (capillary or serum) 1, 2
3. Assess volume status and renal function 2, 3
4. Treat infection appropriately 4, 2
5. Maintain adequate hydration (IV fluids if oral intake compromised) 1, 3

During Infection Treatment:

• Monitor glucose and ketones serially if patient has reduced intake or ongoing illness 1, 2
• Provide alternative glycemic control if needed (typically insulin for severe illness) 2, 3
• Avoid prolonged fasting periods 1

Before Restarting (Minimum 24-48 Hours After Clinical Improvement):

1. Confirm normal oral intake for 24-48 hours 1
2. Mandatory ketone check: must be <0.6 mmol/L 1
3. Verify stable vital signs and improving infection 1
4. Check renal function and electrolytes 2, 3
5. Assess volume status (no orthostatic symptoms) 5, 2

Common Pitfalls to Avoid

Never assume normal glucose means no ketoacidosis—euglycemic DKA can occur with glucose <250 mg/dL or even normal levels. 1, 2 Always check ketones during acute illness in patients on SGLT2 inhibitors. 1, 2

Do not restart dapagliflozin before confirming ketone clearance, even if the patient feels better and glucose is controlled. 1 The drug's effects persist for days after discontinuation. 2

Do not continue dapagliflozin "for cardioprotection" during acute illness—the immediate risk of ketoacidosis and volume depletion outweighs any theoretical cardiovascular benefits during the acute phase. 1

Provide written sick-day rules at discharge instructing patients to stop dapagliflozin during any illness with fever, vomiting, reduced intake, or inability to maintain hydration. 1, 2 Educate patients on ketoacidosis symptoms: nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. 2

Special Considerations for Perioperative Management

For planned surgery, dapagliflozin should be withheld for at least 3 days before major surgery or procedures with prolonged fasting to reduce perioperative metabolic acidosis risk. 6, 2 This is distinct from acute infection management but follows similar principles regarding ketoacidosis prevention. 6