vardenafil-dihydrochloride and Diabetes-Mellitus--Type-1

The association of diabetes-related vascular damage and the role of metabolic factors in erectile dysfunction are well known in the literature. The compounds propionyl-L-carnitine (PLC), L-arginine (L-Arg) and nicotinic acid have numerous metabolic actions which have been reported to improve endothelial function. This study investigated the administration of the combination of these three compounds alone and in association with an inhibitor of 5-phosphodiesterase (5PDE), vardenafil, on endothelial function in diabetic patients with erectile dysfunction.. A total of 40 patients aged between 50 and 60 years with insulin-dependent diabetes (IDDM) for 3-4 years were selected from 509 patients presenting with erectile dysfunction. The patients were randomly subdivided into four groups of ten to be treated for 12 weeks. Group A was administered one sachet each day of test formulation containing PLC, L-Arg and nicotinic acid (Ezerex); group B with one 20 mg capsule of vardenafil (Levitra) twice a week; group C was treated with one sachet each day of the test formulation plus vardenafil 20 mg twice a week. Group D was administered placebo capsules twice weekly. Endothelial function was evaluated by examining flow-mediated dilation (FMD) and erectile function was estimated with the International Index of Erectile Function (IIEF5) questionnaire in all subjects.. At the end of treatment group A showed an increment of 2 points in the IIEF5; group B showed an increment of 4 points; group C, the group which was administered all the treatments, showed an increment of 5 points, and group D, treated with placebo, showed no increment in the IIEF5.. Although there was a small number of subjects in this study the data suggest that the test formulation may improve the endothelial situation in diabetes. The test formulation together with vardenafil was better than the 5PDE inhibitor alone, but further studies are needed to confirm these findings.

Topics: Arginine; Carnitine; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Niacin; Penile Erection; Piperazines; Placebos; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction (ED) affects up to 70% of men with diabetes, occurring with a higher prevalence in those with type 1 diabetes than with type 2 diabetes. Studies investigating treatment of ED in men with diabetes have largely been conducted in a total male population with diabetes. Limited data are available on the efficacy and safety of the potent oral phosphodiesterase-5 inhibitor vardenafil in men with ED and type 1 diabetes.. To evaluate the safety and efficacy of flexible-dose vardenafil therapy in a prospective randomized study in phosphodiesterase 5 inhibitor-naïve subjects with type 1 diabetes and ED.. In this multicenter, double-blind, placebo-controlled clinical trial, phosphodiesterase-5 inhibitor-naïve patients were randomized to receive placebo (N = 149) or flexible-dose (5-20 mg) (N = 153) vardenafil.. Sexual Encounter Profile diary questions 2 and 3, concerning success rates of vaginal insertion and maintenance of erection to allow successful intercourse, respectively.. Vardenafil significantly improved mean success rates for Sexual Encounter Profile 2 and 3 compared with baseline and placebo at 4, 8, and 12 weeks (P < 0.0001, intention to treat and last observation carried forward). These rates were unaffected by stratification into distinct subsets according to the level of HbA(1c) (HbA(1c) < 7%, good glycemic control; HbA(1c) >7- < or = 8%, moderate glycemic control; and HbA(1c) > 8%, poor glycemic control). Vardenafil treatment also significantly improved the Erectile Function domain score (P < 0.0001) of the International Index of Erectile Function compared with placebo, in addition to scores for the other individual domains of the International Index of Erectile Function. The most commonly reported treatment-emergent adverse events were headache (3.1%) and flushing (2.5%), which were mild to moderate and transient in nature.. These data suggest that vardenafil significantly improves erectile function in men with type 1 diabetes and is well tolerated, regardless of the level of glycemic control.

Topics: Adult; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Sexual Behavior; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes.. In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks.. After 12 weeks of treatment, a dose-dependent (P = 0.02) improvement in erections was noted for the GAQ, with 57 and 72% of men taking 10 mg or 20 mg vardenafil, respectively, reporting improved erections, in contrast to 13% after taking placebo (P < 0.0001). For the erectile function domain, dose-dependent (P = 0.03) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo (P < 0.0001). Both vardenafil doses significantly enhanced the rates of successful penetration (P < 0.0001) and successful intercourse (P < 0.0001) compared with placebo. Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity, at each level of plasma HbA(1c), and for type 1 and 2 diabetes. Treatment-emergent adverse events were primarily mild to moderate headache (

Topics: Administration, Oral; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Diabetic nephropathy (DN) is characterized by podocyte damage and increased phosphodiesterase-5 (PDE-5) activity-exacerbating nitric oxide (NO)-cyclic 3',5' guanosine monophosphate (cGMP) pathway dysfunction. It has been shown that PDE-5 inhibition ameliorates DN. The role of podocytes in this mechanism remains unclear. We investigated how selective PDE-5 inhibition influences podocyte damage in streptozotocin (STZ) diabetic rats.. Male Sprague-Dawley rats (250-300 g) were injected with STZ and divided into two groups: (i) STZ control (non-treated, STZ, n=6) and (ii) STZ+vardenafil treatment (10 mg/kg/day, STZ-Vard, n=8). Non-diabetic rats served as negative controls (Control, n=7). Following 8 weeks of treatment, immunohistochemical and molecular analysis of the kidneys were performed.. Diabetic rats had proteinuria, increased renal transforming growth factor (TGF)-β1 expression and podocyte damage when compared with controls. Vardenafil treatment resulted in preserved podocyte cGMP levels, less proteinuria, reduced renal TGF-β1 expression, desmin immunostaining in podocytes and restored both nephrin and podocin mRNA expression. Diabetes led to increased glomerular nitrotyrosine formation and renal neuronal nitric oxide synthase and endothelial nitric oxide synthase mRNA expression, but vardenafil did not influence these parameters.. Our data suggest that a dysfunctional NO-cGMP pathway exacerbates podocyte damage in diabetes. In conclusion, vardenafil treatment preserves podocyte function and reduces glomerular damage, which indicates therapeutic potential in patients with DN.

Topics: Animals; Blotting, Western; Cells, Cultured; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Imidazoles; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphodiesterase 5 Inhibitors; Piperazines; Podocytes; Proteinuria; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfones; Transforming Growth Factor beta1; Triazines; Vardenafil Dihydrochloride