Risk Factors for Genitourinary Infections with SGLT-2 Inhibitors

Risk Factors for Genitourinary Infections with SGLT-2 Inhibitors
David Bunch, Pharm.D., Geritom Medical Inc.

Background: Patients with diabetes are at an increased risk of genitourinary infections (GUI), such as urinary tract infections and genital mycotic infections. The infections have also been described as common side effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor medications. Premarketing clinical trials for SGLT2 inhibitors have suggested a combined absolute risk of 13.9-20.7% for these infections. There is minimal evidence on whether certain patient characteristics could be defined as risk factors for developing GUI.

Purpose: The primary objective of this analysis by Benjamin and Schumacher was to evaluate if hemoglobin A1c at initiation of therapy was a predictor for increased risk of developing a GUI in patients with type 2 diabetes. The secondary objective was to evaluate whether additional factors, such as age, body mass index (BMI), eGFR, fasting plasma glucose, serum sodium, serum potassium or serum creatinine, impacted the risk of developing a GUI with concurrent use of an SGLT2 inhibitor.

Study Design: This study was a retrospective, multicenter cohort analysis that utilized ambulatory care patient data from a total of 42 different clinics in the south and southeastern suburbs of Chicago. Inclusion criteria consisted of patients who were 18 years or older with a diagnosis of type 2 diabetes treated with an SGLT2 inhibitor for at least seven days during a prespecified five year window. Exclusion criteria included those patients who had no laboratory values recorded, a history of GUI in the past year, or a contraindication to SGLT2 inhibitor therapy (pregnancy, eGFR <30mL/min/1.73 m2, and end stage renal disease). A history of GUI was defined as a single instance of GUI confirmed by urinalysis, urinary culture, history of antibiotic or antifungal prescriptions with corresponding physician documentation or appropriate diagnosis code.

Results: The researchers included data from 584 patient charts in their retrospective analysis. Of those, there were 30 (5.14%) patients who developed a GUI after initiating an SGLT2 inhibitor. Baseline A1c was not found to have a significant impact on the incidence of GUI in these patients on SGLT2 inhibitors. The only prespecified secondary outcome that showed statistically significant increased risk of GUI was a lower eGFR [79.28 vs. 73.37 mL/min/1.73 m2, P=0.0361]. BMI, fasting glucose, potassium, sodium, and serum creatinine were not statistically significant indicators, nor was increased risk associated with any one particular SGLT2 inhibitor. Male sex was found to have a lower incidence of GUI [7 vs. 23, P=0.0019], which was expected due to previously documented risk for GUI being higher in females on SGLT2 ihibitors at baseline. A post-hoc analysis that included the 30 patients who were initially excluded due to a history of GUIs within one year of SGLT2 therapy found that 13 (43.3%) of these patients experienced a GUI subsequent to SGLT2 inhibitor initiation, making prior history of GUI within one year the largest risk factor in this analysis. Of the 43 total patients diagnosed with a GUI in the post-hoc analysis, 23 (55%) were diagnosed with a fungal infection, 19 (45%) as presumed bacterial infection, and one of these was presumed to have both a fungal and bacterial GUI. The average time to GUI was 336 days [SD 323 days, median 247 days, range 5-1190 days].

Conclusions: The results of this retrospective, multicenter cohort study demonstrated that baseline A1c had no effect on the risk of developing a GUI on SGLT2 inhibitor therapy. A lower eGFR was the only secondary outcome that showed a statistically significant increased risk for a GUI while taking an SGLT2 inhibitor. Based on the post-hoc analysis, the largest risk factor to take into account for GUI on SGLT2 inhibitors is a prior history of GUI.

Key Point: Baseline A1c has no significant effect on GUI risk in patients on SGLT2 inhibitors. However patients with a decreased eGFR and prior history of GUI may be at higher risk for these infections if started on an SGLT2 inhibitor and should be educated on their risk and risk reduction strategies when initiating these medications.

References:

  1. Benjamin T, Schumacher C. Characterization of risk factors for genitourinary infections with sodium‐glucose cotransporter‐2 inhibitors. Pharmacotherapy. 2020;40(10):1002-1011.