Should dapagliflozin be continued during an acute infection?

Dapagliflozin Should Be Stopped During Acute Infection

Dapagliflozin and other SGLT2 inhibitors should be discontinued during acute infections and patients should follow "sick day rules." This recommendation is based on the significant risks of dehydration, diabetic ketoacidosis (DKA), and acute kidney injury during illness 1.

Key Risks During Infection

The primary concerns with continuing dapagliflozin during infection include:

• Diabetic ketoacidosis (DKA): Risk increases during illness, particularly in patients with insulin deficiency. The FDA label reports DKA occurred in 27/8574 patients on dapagliflozin versus 12/8569 on placebo in major trials 2
• Dehydration: SGLT2 inhibitors cause osmotic diuresis, which is particularly dangerous when patients have reduced oral intake or increased fluid losses during infection
• Acute kidney injury: Renal function can deteriorate rapidly during illness, and SGLT2 inhibitors affect renal hemodynamics 1

Clinical Algorithm for Management

Before infection occurs:

• Educate patients about sick day rules
• Instruct them to stop dapagliflozin at first signs of infection or illness
• Provide clear instructions about when to resume therapy

During active infection:

1. Discontinue dapagliflozin immediately
2. Monitor renal function closely (creatinine, eGFR)
3. Assess hydration status and ensure adequate fluid intake
4. Monitor for signs of DKA (nausea, vomiting, abdominal pain, altered mental status)
5. Check urine or blood ketones if DKA is suspected
6. Continue insulin therapy if applicable (never stop insulin) 1

After infection resolves:

• Resume dapagliflozin only when patient is eating/drinking normally
• Confirm stable renal function before restarting
• Ensure patient is adequately hydrated

Important Caveats

Avoid initiating dapagliflozin during respiratory illness - this is explicitly contraindicated in guidelines 1. The drug should not be started in acutely ill patients.

Special surgical considerations: Discontinue dapagliflozin 3-4 days before scheduled surgery, during critical illness, or during prolonged fasting to minimize DKA risk 3.

Evidence Nuances

While recent research (DARE-19 trial) showed dapagliflozin was "well tolerated" when initiated in hospitalized COVID-19 patients 4, 5, and the DEFENDER trial showed no excess mortality in critically ill patients with acute organ dysfunction 6, these research findings do not override established guideline recommendations for routine clinical practice. These trials involved intensive monitoring in controlled settings that is not feasible in outpatient management. The 2020 Lancet guidelines remain the standard of care for routine practice 1.

The guideline recommendation to stop SGLT2 inhibitors during illness is based on the precautionary principle - the potential harms (DKA, dehydration, AKI) outweigh uncertain benefits during acute infection, particularly in outpatient settings where close monitoring is limited.