Management of Urinary Tract Infections in Patients Taking SGLT-2 Inhibitors

Introduction to SGLT-2 Inhibitors and UTI Risk

The American Diabetes Association recommends temporarily discontinuing SGLT-2 inhibitors during acute urinary tract infections (UTIs) and antibiotic treatment, and resuming after resolution of the infection, as UTIs are more common in patients taking SGLT-2 inhibitors, with a reported incidence of 33.49% vs 11.72% in non-SGLT-2 inhibitor users 1

Patients taking SGLT-2 inhibitors should be monitored for signs of dehydration and volume depletion, hyperglycemia requiring alternative management, progression to pyelonephritis or urosepsis, and euglycemic diabetic ketoacidosis (a rare but serious complication) 1
High-risk patients, including those with a history of recurrent UTIs, should be identified, as they may require closer monitoring and alternative management strategies, including consideration of discontinuing SGLT-2 inhibitors in patients with recurrent or severe UTIs 1

SGLT-2 inhibitors can be used in patients with an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m², but for patients with eGFR <45 mL/min/1.73 m², SGLT-2 inhibitors have reduced glucose-lowering efficacy but may still provide cardiorenal benefits 1
SGLT2 inhibitors can be continued at lower eGFR levels once initiated, according to Kidney International 2
Expect an initial "eGFR dip" of 3-5 mL/min/1.73 m² in the first 4 weeks, and monitor eGFR more frequently when <60 mL/min/1.73 m², with recommendations to adjust insulin or insulin secretagogues to avoid hypoglycemia, and provide hygienic counseling to prevent genital mycotic infections 3, 4

Patients should be educated on early recognition of UTI symptoms, importance of adequate hydration, and implementation of the "STOP DKA" protocol during illness, which includes stopping the SGLT2 inhibitor, testing for ketones, maintaining fluid and carbohydrate intake, and using insulin as needed, to prevent euglycemic diabetic ketoacidosis and other complications 1
Temporarily withhold SGLT2 inhibitors during periods of prolonged fasting, before major surgery, during critical medical illness, or during acute illness with risk of dehydration, and implement "STOP DKA" protocol during acute illness 5, 4, 3

SGLT2 inhibitors should be initiated in patients with type 2 diabetes and chronic kidney disease with eGFR ≥20 mL/min/1.73 m², independent of HbA1c or the need for additional glucose lowering, as recommended by Kidney International and the American College of Cardiology 2, 6, 7, 8
High priority for SGLT2 inhibitor initiation is given to patients with albuminuria (ACR ≥200 mg/g) or heart failure, as recommended by Kidney International and the Journal of the American College of Cardiology 6, 7, 8
The preferred agents with proven cardiovascular and renal benefits are Canagliflozin 100 mg daily, Dapagliflozin 10 mg daily, and Empagliflozin 10 mg daily, as recommended by Kidney International 6
If a patient is on insulin or sulfonylureas, the dose should be reduced by 50% or discontinued if on minimal dose, and the total daily insulin dose should be reduced by approximately 20%, according to the Journal of the American College of Cardiology 8
If a patient is on diuretics, the dose should be considered for reduction to prevent excessive volume depletion, as recommended by the Journal of the American College of Cardiology and Kidney International 6, 8

Baseline eGFR and albuminuria should be measured, and volume status and risk for volume depletion should be assessed, according to Kidney International 6
Hypoglycemia risk should be evaluated, especially if the patient is on insulin or sulfonylureas, as recommended by the Journal of the American College of Cardiology 8
Patients should be monitored for signs of volume depletion, genital mycotic infections, and hypoglycemia, according to Kidney International and the Journal of the American College of Cardiology 6, 8
Kidney function should be monitored periodically, with frequency based on baseline eGFR, as recommended by Kidney International 2

SGLT2 inhibitors provide cardiovascular and renal benefits, including reduced risk of heart failure hospitalizations, kidney disease progression, cardiovascular mortality, and all-cause mortality, as reported by the American College of Cardiology and the American Diabetes Association 9, 3, 10
Cardiovascular and renal benefits of SGLT2 inhibitors persist down to eGFR of 30 mL/min/1.73 m², independent of glucose-lowering effects, according to the American Diabetes Association and the American College of Cardiology 9

For patients with type 2 diabetes and eGFR <45 mL/min/1.73 m², consider GLP-1 receptor agonists as preferred agents for glycemic control, as recommended by the American Diabetes Association and the American College of Cardiology 11, 9
Canagliflozin, Empagliflozin, and Dapagliflozin are not recommended for glycemic control when eGFR <45 mL/min/1.73 m², as approved by the FDA and reported by the American College of Cardiology 8, 7
SGLT2 inhibitors may still be appropriate for cardiorenal protection despite minimal HbA1c reduction, according to the American Heart Association 3
SGLT2 inhibitors are not recommended in kidney transplant recipients due to immunosuppression and potentially increased risk for infections, and initiating SGLT2 inhibitors below eGFR threshold of 20 mL/min/1.73 m² is not recommended, but can be continued if already initiated, according to Kidney International guidelines 4, 5, 2, 12