Sodium-glucose cotransporter-2 inhibitors and vulvovaginal pruritus: Insights from a cox proportional hazards model analysis

Summary: Abstract Body: Vulvovaginal (VV) pruritus is distressing with numerous etiologies and has been shown to be more prevalent in individuals with diabetes mellitus (DM).2 This study investigates the association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and VV pruritus in patients with type 2 diabetes mellitus (T2DM). Using the TriNetX US Collaborative Network, we identified females with T2DM across 64 healthcare organizations. Cohorts included SGLT2i users (n=832,692) and non-users (n=6,793,437). Patients who developed candidiasis (including VV candidiasis) after starting an SGLTi were excluded. Cox proportional hazards regression, adjusting for demographics, comorbidities, and medications, assessed the primary outcome of vulvovaginal pruritus (ICD-10 code L29.2) within three years. SGLT2 inhibitor use was significantly associated with an increased risk of VV pruritus, with a Hazard Ratio (HR) of 1.9 (p=0.014). Incidence rates were higher among users (0.16%) versus non-users (0.07%), yielding a risk difference of 0.09% (95% CI: 0.05%, 0.13%; p<0.0001). Additionally, patients identifying as white (HR 0.8, p=0.020) and patients taking ACE inhibitors (HR 0.4, p=0.009) had lower rates of VV itch. These findings highlight a notable association between SGLT2i use and VV pruritus, potentially mediated by glucosuria-induced yeast overgrowth and microbiota changes. Given the known association between SGLTi and increased risk of VV candidiasis, it is possible that patients with SGLTi associated pruritis have undiagnosed yeast infections or that the pruritis is mediated through another unknown mechanisms.4,7 Thus, it is crucial to conduct further prospective studies with evaluation of bacterial and fungal cultures and measurement of VV pH in patients on SGLTi to further elucidate the nature of SGLTi associated pruritis. Jessica Saoub¹, Sarahi Mera¹, Amylee Martin², Ashley Elsensohn², Daniel Novak¹ 1. Medicine, University of California Riverside, Riverside, CA, United States. 2. Dermatology, Loma Linda University, Loma Linda, CA, United States. Clinical Research: Epidemiology and Observational Research