Effects of chronic administration of Vardenafil on endothelial function in patients with type 2 diabetes mellitus. A longitudinal, randomized, placebo-controlled, double blind, non-sponsored clinical trial
D. Santi, A. Guidi, A. Granata, M. Simoni & C. Carani
Introduction: The endothelium produces molecules regulating vascular function, such as nitric oxide (NO). NO protects blood vessels from endogenous injury and causes vasodilation through activation of second messengers. In diabetes mellitus (DM), hyperglycemia provokes oxidative stress, reduction of NO and increased synthesis of vasoconstrictors (e.g. endothelin). Cyclic nucleotide phosphodiesterases (PDEs) are enzymes, controlling the rate of degradation of second messengers. In short-term studies PDE-5 inhibitors showed promising results on endothelial function parameters. No data about chronic treatment in diabetic subjects are available.
Aim: To investigate if chronic treatment with Vardenafil for six months can prevent or delay the deterioration of systemic endothelial function in patients with type 2 DM.
Methods: Longitudinal, randomized, placebo-controlled, double-blind clinical trial involving men with type 2 DM. Study duration: 52 weeks including enrollment (4 weeks), treatment (24 weeks), follow-up (24 weeks). Treatment: 2×10 mg/day of Vardenafil/placebo. Parameters: andrological and instrumental examination and blood sampling performed at each visit. Primary end-point: serum endothelin-1. Sample size: 53 patients per arm.
Results: Interim analysis of blinded data: of 35 patients enrolled so far, 18 (51.43%) completed the treatment phase, 12 (34.29%) ended the study. Five patients dropped-out (14.29%). All patients, had a good adherence to treatment (mean of tablets taken: 92.2%). Glycated hemoglobin, considering 18 patients who ended the treatment phase, improved in seven (38.9%), worsened in 2 (11.1%) and remained elevated in five (27.8%) patients. Flow-mediated dilation (FMD, 13 patients) improved in 1 (7.7%), worsened in three (23.1%) and persisted elevated in three (23.1%) patients. Intima-media thickness (IMT) and IIEF-15 improved in 1 patient. Endothelin-1 and other serum parameters will be measured at the end of the study.
Conclusion: Intervention per se results in variations of glycated hemoglobin and FMD values (improvement/impairment) in 50% and 30.8% of patients, respectively but does not seem to influence IMT and IIEF-15 values.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.