Undiagnosed prediabetes status is associated with a reduced effectiveness of phosphodiesterase type 5 inhibitors in men with erectile dysfunction

The efficacy of phosphodiesterase type 5 inhibitors (PDE5i) in patients with erectile dysfunction (ED) and undiagnosed prediabetes (PreDM) has been scantly analysed. We aimed to assess rates of and predictors of response to oral treatment in a cohort of ED men naïve for PDE5i with either normo-glycaemia or PreDM or diabetes mellitus (DM). Complete data from 466 men were analysed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF) at baseline and after 3 months of PDE5i treatment. Treatment response was evaluated using the minimal clinically important difference (MCID) (mild: +2; moderate: +5; severe: +7 from baseline IIEF-EF). PreDM status was defined as for the American Diabetes Association (2015) criteria. Descriptive statistics and logistic regression models tested the association between clinical predictors and MCID response. Overall, 253 (56.7%), 105 (23.5%) and 88 (19.7%) patients had normo-glycaemia (=controls), PreDM and DM, respectively. Diabetic and PreDM men were older, had higher BMI, higher CCI scores and lower total testosterone (tT) (all p < 0.01) compared to controls. Median baseline IIEF-EF was lower both in PreDM (14.0 vs. 18.0; p < 0.05) and DM patients (10.0 vs. 18.0; p < 0.001) than in controls. IIEF-EF improved in all groups after treatment (all p < 0.001), but scores were higher in controls compared to both PreDM and DM men at 3-mos assessment (26.0 vs. 20.0 vs. 17.5, respectively; all p < 0.001). Controls more frequently achieved significant MCID than both PreDM and DM patients (65.3 vs. 22.9 vs. 11.8%, respectively; p < 0.01). Age (p < 0.001), baseline IIEF-EF (p < 0.001), and DM status (p = 0.02) were independently associated with MCID. In conclusion, patients with undiagnosed PreDM depicted lower rates of response to PDE5i than normoglycemic men. These findings suggest that even milder forms of glucose impairment are associated with a poorer PDE5i effectiveness in men with ED.