Why should dapagliflozin (Sodium-Glucose Cotransporter 2 inhibitor) be held in a patient with a urinary tract infection (UTI) and a history of diabetes?

Why Dapagliflozin Should Be Held During UTI

Dapagliflozin should be temporarily discontinued during a urinary tract infection because acute illness—particularly infections with fever, reduced oral intake, or systemic symptoms—significantly increases the risk of euglycemic diabetic ketoacidosis and volume depletion, both of which are serious complications of SGLT2 inhibitor therapy. 1

Primary Rationale: Sick Day Management Protocol

The fundamental reason to hold dapagliflozin during UTI relates to established "sick day rules" for SGLT2 inhibitors:

• Temporarily discontinue dapagliflozin during any acute illness, particularly when patients experience reduced food and fluid intake, fever, vomiting, or diarrhea. 1
• The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines specifically recommend withholding SGLT2 inhibitors during critical medical illness when patients are at greater risk for ketosis. 2
• UTIs requiring hospitalization or causing systemic symptoms qualify as intercurrent illness requiring drug discontinuation. 1

Risk of Euglycemic Diabetic Ketoacidosis

The most serious concern during acute illness is ketoacidosis:

• Monitor for diabetic ketoacidosis (DKA) even with normal blood glucose levels, as this is a serious risk during illness in patients taking SGLT2 inhibitors. 1
• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels when taking dapagliflozin, and may present with nonspecific symptoms like malaise, nausea, vomiting, or abdominal pain. 3, 1
• Factors that trigger DKA include intercurrent illness (such as UTI), reduced food and fluid intake, reduced insulin doses, and the continued use of SGLT2 inhibitors during illness. 3

Volume Depletion Risk

UTIs compound the volume depletion risk inherent to SGLT2 inhibitors:

• The diuretic effect of dapagliflozin combined with illness-related fluid losses (from fever, reduced intake during UTI symptoms) significantly increases risk of hypovolemia. 1
• SGLT2 inhibitors cause clinically significant volume depletion, for which older adults and those with concurrent diuretic therapy are at greater risk. 3
• Assess volume status carefully during any acute illness in patients on dapagliflozin. 1

The UTI-SGLT2 Inhibitor Relationship

While UTI itself is a known adverse effect of dapagliflozin, the relationship is bidirectional:

• Treatment with dapagliflozin is accompanied by a slightly increased risk of urinary tract infection (5.3-5.7% vs 3.7% with placebo), though infections are generally mild to moderate and clinically manageable. 4, 5
• SGLT2 inhibitors increase urinary glucose levels, creating a more favorable environment for bacterial growth, with women more affected (76.2%) than men. 5, 6
• Once UTI develops, continuing the drug during active infection perpetuates glucosuria and may impair infection resolution while simultaneously increasing DKA risk. 1, 4

Clinical Algorithm for Holding Dapagliflozin

When to hold:

• Any UTI with systemic symptoms (fever, chills, flank pain) 1
• UTI with reduced oral intake or inability to maintain hydration 1
• UTI requiring hospitalization 3
• UTI in patients with recurrent or severe urinary tract infections 3

Critical monitoring during UTI:

• Check blood or urine ketones if patients develop malaise, nausea, or vomiting during UTI treatment. 1
• Maintain at least low-dose insulin in insulin-requiring individuals even when dapagliflozin is held, as complete insulin cessation increases DKA risk. 1
• Do not reduce insulin doses excessively when holding dapagliflozin during illness, as this combination significantly elevates ketoacidosis risk. 1

When to restart:

• Resume dapagliflozin only after patient has recovered from acute illness and normal oral intake is re-established. 1
• Ensure UTI symptoms have resolved and patient is maintaining adequate hydration before restarting. 1

Patient Education Requirements

• Counsel patients to stop dapagliflozin immediately when they become sick with UTI symptoms and contact their healthcare provider. 1
• Instruct patients to seek immediate medical attention if they develop symptoms of DKA (malaise, nausea, vomiting, abdominal pain) or severe genital/urinary infections during UTI treatment. 1
• Educate patients on specific triggers that necessitate drug discontinuation, including reduced ability to eat or drink normally during UTI. 1

Common Pitfalls to Avoid

• Do not continue dapagliflozin during symptomatic UTI simply because blood glucose remains controlled—the DKA risk is independent of glucose levels. 1
• Do not stop insulin therapy when holding dapagliflozin during UTI, as this dramatically increases ketoacidosis risk. 1
• Do not restart dapagliflozin before confirming adequate oral intake and UTI symptom resolution. 1