Association of tirzepatide with erectile dysfunction in people with type 2 diabetes.

AIMS: To evaluate the association between tirzepatide and the risk of developing erectile dysfunction (ED) in men with type 2 diabetes (T2D), compared with sitagliptin, injectable semaglutide, and dulaglutide. METHODS: This retrospective cohort study used the TriNetX global health research network from May 13, 2022 to May 17, 2025. Male patients aged 18-70 with T2D and no prior ED were included. Three 1:1 propensity score-matched comparisons were conducted: tirzepatide vs. sitagliptin, injectable semaglutide, or dulaglutide. The outcome was a diagnosis of ED or prescription of a PDE-5 inhibitor. RESULTS: Tirzepatide was associated with a significantly reduced risk of ED across all comparisons. Risk ratios (RR) for the composite outcome of ED diagnosis or PDE-5 inhibitor use were: tirzepatide vs. sitagliptin: RR, 0.70 (95 % CI: 0.64,0.76); tirzepatide vs. injectable semaglutide: RR, 0.67 (95 % CI: 0.62,0.72); tirzepatide vs. dulaglutide: RR, 0.55 (95 % CI: 0.51,0.59). All comparisons were statistically significant (p < 0.001). CONCLUSIONS: Tirzepatide was associated with a lower risk of ED in men with T2D compared to sitagliptin, injectable semaglutide, and dulaglutide. Randomized trials are needed to confirm these findings and explore potential mechanisms.