Effects of tadalafil and SGLT2 inhibitors on erectile and diastolic functions in men with metabolic syndrome: A randomized controlled study

Abstract

Background Erectile dysfunction (ED) is an early manifestation of systemic endothelial dysfunction and is increasingly linked to subclinical myocardial impairment. Whether sodium – glucose cotransporter-2 inhibitors (SGLT2i), alone or combined with phosphodiesterase-5 inhibition, confer simultaneous cardio-sexual benefit in men with metabolic syndrome remains unknown. This study aimed to compare the effects of tadalafil, SGLT2i and their combination on erectile and left ventricular diastolic functions in patients with metabolic syndrome (MetS).Methods In this prospective, randomized, assessor-blinded, parallel-group trial, 60 men with metabolic syndrome and ED were assigned 1:1:1 to tadalafil 5 mg daily, an SGLT2 inhibitor (dapagliflozin or empagliflozin 10 mg daily), or their combination for 3 months. The primary endpoint was change in Erectile function domain of the International Index of Erectile Function (IIEF-EF, 6 items). Secondary endpoints included changes in echocardiographic diastolic indices (ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (e′) ‘E/e′’, isovolumic relaxation time ‘IVRT’, deceleration time, and pulmonary artery systolic pressure ‘PASP’), the correlation between ΔIIEF-EF (Change from baseline) and ΔE/e′, and independent predictors of erectile improvement.Results All three regimens significantly improved IIEF-EF scores (all p < 0.01). Between-group analysis showed a significant difference in ΔIIEF-EF (p = 0.049), with combination therapy superior to SGLT2 inhibitor monotherapy (p = 0.043). Combination therapy improved all diastolic parameters, including E/e′, IVRT, deceleration time, and PASP; tadalafil monotherapy improved PASP only, whereas SGLT2 inhibitor monotherapy improved E/e′, IVRT, and deceleration time but not PASP. ΔIIEF-EF correlated strongly with ΔE/e′ (ρ = −0.617, p < 0.001). Multivariate regression identified younger age (β = −0.367), non-smoking status (β = −0.240), and greater ΔE/e′ reduction (β = −0.264) as independent predictors of erectile improvement.Conclusions Combined tadalafil and SGLT2 inhibitor therapy was associated with greater improvement in erectile and diastolic functions in men with metabolic syndrome, supporting a vasculoprotective dual-therapy strategy. Improvement in left ventricular filling pressure independently predicts erectile recovery, underscoring shared vascular pathophysiology. These findings support a link between endothelial recovery and sexual function.