Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population‐based study of older women and men with diabetes

Abstract

Aims The objective of the study was to quantify the association between SGLT2 inhibitors and genital mycotic infection and between SGLT2 inhibitors and urinary tract infection (UTI) within 30 days of drug initiation among older women and men. Materials and methods This was a retrospective cohort study using linked administrative databases of women and men with diabetes, aged 66 years or older, in Ontario, Canada. We compared the incidence of genital mycotic infection or UTI within 30 days between new users of an SGLT2 inhibitor and of a dipeptidyl‐peptidase‐4 (DPP4) inhibitor. Results We identified 21 444 incident users of SGLT2 inhibitor and 22 463 incident users of DPP4 inhibitor. Among SGLT2 inhibitor users, there were 8848 (41%) women and the mean age at index was 71.8 ± 5 (SD) years. After adjusting for propensity score, age, sex and recent UTI, there was a 2.47‐fold increased risk of genital mycotic infection with incident use of SGLT2 inhibitors (adjusted hazard ratio (HR), 2.47; 95% confidence interval (CI), 2.08‐2.92; P < 0.001) within 30 days compared to incident use of DPP4 inhibitors. For UTI, the adjusted HR was 0.89 (95% CI, 0.78‐1.00; P = 0.05). Conclusions Incident use of SGLT2 inhibitors among older women and men is associated with increased risk of genital mycotic infections within 30 days; there is no associated increased risk of UTI. These findings from a real‐world setting provide evidence of the potential harms of SGLT2 inhibitors.

Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes

“…The most common side effects reported with dapagliflozin 5 mg across the DEPCIT clinical trial programme for T1DM were an increased incidence of genital mycotic infections (10-16% compared with 2-3% for placebo) and urinary tract infections (UTIs) (7-12% compared with 4-8% for placebo). The increased risk of genital mycotic infections associated with SGLT2 inhibitors has also been reported in a real-world setting [51]. Although these infections have the potential to significantly impact quality of life, most are mild-to-moderate infections that can be easily managed and do not necessitate dapagliflozin discontinuation.…”

Sodium-glucose co-transporter-2 inhibitors: peculiar “hybrid” diuretics that protect from target organ damage and cardiovascular events

“…Besides these multiple CV benefits, potential side effects of these drugs also emerged from RCTs. More specifically, in addition to the potential risk of AKI linked to the volume depletion in susceptible individuals with an inadequate fluid intake, an increased risk of genital mycotic infections has been reported in RCTs, while the risk of urinary tract infections did not increase significantly [74]. Even though the several RCTs have provided a well-defined safety profile, few other rare and debated potential side effects have been reported [75]: euglycaemic ketoacidosis, especially in T1DM or during acute illness, bone fractures, Fournier's gangrene, lower limb amputations, the latter three without agreement between RCTs and not confirmed in real-world evidence [76].…”

A hypothesis for why sodium glucose co‐transporter 2 inhibitors have been found to cause genital infection, but not urinary tract infection

“… Note: Study details for observational studies are based on propensity score matched results except for Lega et al, which did not use propensity score matching. Note the duration of follow‐up are approximations based on the reported data.…”

“…Because clinical trials are often underpowered to detect adverse events, and often exclude patients at highest risk, observational studies using real‐world data with much larger sample sizes than is possible in clinical trials have been conducted to confirm that there is truly no increased risk. Three observational studies, including nearly 100 000 patients who received an SGLT2 inhibitor, have been completed, and none have detected an increased risk of UTI relative to a comparator diabetes medication (Table ) …”