Urinary tract and genital infections with dapagliflozin and empagliflozin across type 2 diabetes, heart failure, and chronic kidney disease: An indication- and sex-stratified disproportionality analysis of eudravigilance reports

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM), chronic heart failure (CHF), and chronic kidney disease (CKD). Although their cardiovascular and renal benefits are well established, urogenital infections remain a relevant safety concern. Comparative post-marketing data on dapagliflozin (DAPA) and empagliflozin (EMPA) across therapeutic indications are limited. A retrospective pharmacovigilance analysis of the EudraVigilance database (January 2021-July 2025) was conducted using a case/non-case approach. Cases were defined as individual case safety reports (ICSRs) containing at least one urogenital infection-coded reaction and a confirmed indication (T2DM, CHF, or CKD). The primary analysis was restricted to reports originating from the European Economic Area (EEA), where reporting rules are identical for both drugs; reports with unspecified patient age were excluded. Among 16,102 EEA ICSRs, 8156 adult reports with a confirmed indication were analyzed, of which 1109 met the case definition. Non-EEA reports were analyzed separately as a sensitivity analysis. Urogenital infection reporting did not differ between DAPA and EMPA, overall (ROR 0.91; 95% CI 0.80-1.03) or within any indication (T2DM: 13.9% vs 14.9%, ROR 0.92; 95% CI 0.79-1.07; CHF: 11.5% vs 12.6%, ROR 0.90; 95% CI 0.69-1.18; CKD: 11.0% vs 6.7%, ROR 1.73; 95% CI 0.75-3.99). For both drugs, reporting was higher in T2DM than in CHF (DAPA ROR 1.25; 95% CI 1.00-1.56; EMPA ROR 1.22; 95% CI 0.99-1.51), a difference confined to female patients (DAPA 1.38; EMPA 1.56) and, in the endpoint disaggregation, to genital mycotic infections (DAPA 2.24; EMPA 1.79) rather than non-mycotic urogenital infections. Female sex was the strongest determinant of urogenital infection reporting for both drugs (ROR female/male 1.85 for DAPA and 1.58 for EMPA). In non-EEA reports, an apparent excess of urogenital infection reporting with DAPA over EMPA (ROR 1.85; 95% CI 1.59-2.16) was explained by a different composition of the reports forwarded for the two drugs rather than by a drug effect. Urogenital infection reporting with SGLT2 inhibitors depends on indication and sex rather than on the molecule, and between-drug comparisons in EudraVigilance are sensitive to the geographic origin of reports.