Real-world evidence of urinary tract infections and genital tract infections with sodium-glucose cotransporter-2 inhibitors (SGLT2i) alone or in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) in individuals with type-2 diabetes mellitus in India

BACKGROUND: Type 2 diabetes mellitus (T2D) is a growing global and Indian health challenge. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), increasingly used in India, are linked to higher genitourinary infection (UTI/GTI) rates in people with T2D worldwide, yet real-world evidence in India remains limited. The impact of combining SGLT2i with Dipeptidyl peptidase-4 inhibitors (DPP4i) on infection risk also requires investigation in this setting. METHODS: This multicenter, cross-sectional, observational study enrolled adults with T2D across India from June 15 to September 30, 2023. Data on UTI/GTI incidence, antidiabetic medications, demographics, and comorbidities were collected. Logistic regression and propensity score matching evaluated associations between SGLT2i, DPP4i, their combination, and UTI/GTI risk. RESULTS: (SD 4.8). Urogenital infection incidence is 11.3% (95% CI: 10.8%-11.8%), with GTI at 5.8% (95% CI: 5.4%-6.2%) and UTI at 7.1% (95% CI: 6.6%-7.4%). Females showed higher rates than males (13.3% vs. 9.7%, p < 0.001). SGLT2i users had a significantly elevated infection rate (13.2%, 95% CI: 12.5%-13.8%) compared to non-users (7.2%, 95% CI: 6.5%-8.0%, p < 0.001). Subjects in SGLT2i with DPP4i (no other OADs) had the lowest infection rate (4.4%, 95% CI: 2.7%-6.1%, p < 0.001). Regression analysis (61% accuracy) revealed that SGLT2i increased infection odds by 2.89 (95% CI: 1.69-2.96, p < 0.001), but adding DPP4i reduced it to 1.62 (95% CI: 1.36-1.92, p < 0.001). CONCLUSIONS: This first large-scale, real-world study in India confirms a higher UTI/GTI incidence in people with T2D on SGLT2i. Notably, combining DPP4i with SGLT2i was associated with a lower observed incidence of urogenital infections compared with SGLT2i without DPP4i. These findings are observational and require prospective validation. These results highlight the need for tailored therapeutic strategies in Indian T2D management. CLINICAL TRIAL NUMBER: not applicable.