Genital fungal infections in type 2 diabetes: Clinical, behavioral, and microbiota correlates of SGLT2 inhibitor therapy

Abstract

Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors improve cardiometabolic outcomes in type 2 diabetes mellitus (T2DM) but increase susceptibility to genital fungal infections. Data integrating clinical, behavioral, immune, and microbiota determinants remain limited. Methods: We conducted a cross-sectional study of 100 adults with T2DM (50 SGLT2 users, 50 non-users). Demographics, clinical parameters, and infection symptoms were recorded. Behavioral factors (awareness, hygiene) were assessed by questionnaire. Laboratory evaluation included glycemic stress markers (HbA1c, fructosamine, AGEs), inflammatory and immune markers (CRP, IL-6, IL-8, TNF-α, β-D-glucan, CD4/CD8 ratio, neutrophil oxidative burst), and microbiota profiling (fungal load by qPCR, Lactobacillus abundance, dysbiosis index). Results: Infection prevalence was higher in SGLT2 users (36% vs. 12%; OR 4.12, 95% CI 1.47–11.56, p = 0.009). Common symptoms included itching (77.8%), redness (61.1%), and discharge (50.0%). Awareness was low (64% unaware), and 44% reported inadequate hygiene. Biomarker analysis showed reduced TNF-α (p = 0.033) and impaired neutrophil oxidative burst (p = 0.010) in infected patients. Glycemic stress markers were not significantly different. Infected patients had higher fungal load (~100,000 vs. 1,000 copies/mL), reduced Lactobacillus (20.7% vs. 42.1%), and elevated dysbiosis index (6.7 vs. 3.2; all p < 0.001). Conclusion: SGLT2 inhibitor use is associated with a fourfold higher risk of genital fungal infections in T2DM. Microbiota disruption and innate immune dysfunction, rather than glycemic stress, appear central to susceptibility. Patient education on hygiene and early recognition may mitigate risk.