Phosphodiesterase 5 inhibitor use and incident diabetic retinopathy in men with erectile dysfunction and type 2 diabetes: a propensity-matched cohort study

Abstract Background/objectives To evaluate the association between phosphodiesterase type 5 inhibitor (PDE5I) use and incident diabetic retinopathy (DR) among men with erectile dysfunction (ED) and type 2 diabetes (T2D). Subjects/methods Male patients aged ≥50 years with ED and T2D were identified from the TriNetX global electronic health record network. Patients receiving PDE5I were compared with non-users. After 1:1 propensity score matching for demographic, systemic, laboratory and treatment-related variables, 1823 patients were included in each cohort. Follow-up extended for up to seven years. Outcomes were identified using ICD-10 and procedural codes and analysed using Kaplan-Meier survival analysis and Cox proportional hazards models. Ophthalmologic follow-up was evaluated as a negative-control outcome to assess surveillance bias. Results During follow-up, PDE5I use was associated with a lower incidence of DR overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] [0.71, 0.96]; p = 0.0139; adjusted p = 0.0626) and proliferative diabetic retinopathy (PDR; HR 0.35, 95% CI [0.21, 0.59]; p < 0.0001; adjusted p < 0.0009). After correction for multiple comparisons, only the association with PDR remained statistically significant (adjusted p < 0.0009). No significant differences were observed for diabetic macular oedema, intravitreal injections, or laser photocoagulation. Rates of ophthalmologic follow-up were comparable between groups (HR 0.93, 95% CI [0.84, 1.02]; p = 0.1072). Conclusions In men aged ≥50 years with ED and T2D, PDE5I use was associated with a lower observed incidence of PDR, while a nominal association with overall DR was also observed. These findings identify an association between PDE5I use and DR outcomes that warrants further evaluation in prospective studies.