Assessment of the Efficacy of Combination Therapy with Folic Acid and Tadalafil for the Management of Erectile Dysfunction in Men with Type 2 Diabetes Mellitus

Abstract

Introduction Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated. Aim To evaluate the efficacy and safety of combination therapy with folic acid and tadalafil for the management of ED in men with type 2 diabetes mellitus. Methods Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10 mg every other day plus folic acid 5 mg daily and group B received tadalafil 10 mg every other day plus placebo daily for 3 months. The mean International Index of Erectile Function (IIEF) scores before and after treatment in each groups were recorded. Men with diagnosis of psychological ED, spinal cord injury, or who used folic acid in the past 3 months and patients with any contradiction for use of PDE5Is were excluded. Main Outcomes Measures The cross tabulation and independent t-test were used to evaluate the difference between baseline characteristic of the patients in the two groups. Wilcoxon signed-ranks test and Mann–Whitney U-test were used to evaluate the IIEF score and also its changes before and after treatment in the two groups. Results The mean IIEF scores before and after treatment were 11.65 ± 2.67 and 16.80 ± 4.03 in group A (P < 0.001) and 12.70 ± 2.31 and 14.37 ± 2.17 in group B (P < 0.001), respectively. The difference of mean IIEF score after treatment between the two groups was significant (16.80 ± 4.03 vs. 14.37 ± 2.17 in groups A and B, respectively) (P = 0.002). Also, the mean IIEF score was significantly increased in group A as compared with group B (5.14 ± 3.84 vs. 1.68 ± 0.99 in groups A and B, respectively) (P < 0.001). Both folic acid and tadalafil were well tolerated by all the patients. Conclusion Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe.

Association between serum folic acid level and erectile dysfunction

“…Because FA has a key role in Hcys metabolism (Mattson & Shea, 2003), the mechanism of ED might be related to the metabolism of Hcys influenced by FA deficiency. Hoch et al (2010) found a reasonable association between serum FA deficiency and ED, as did other authors (Hamidi Madani et al, 2013;Yan et al, 2014). FA deficiency triggers endothelial apoptosis by impairing the process of DNA repair (Pogribny et al, 1995).…”

“…Hamidi Madani et al (2013)found FA supplementation therapy to be clinically useful, and the IIEF scores were three times higher in diabetic patients with ED taking tadalafil and FA in combination than in those taking tadalafil monotherapy in a 3-month therapy setting. In a prospective, randomised, double-blind, placebo-controlled study, Agostini et al (2006) included 176 patients with concurrent type 2 DM and ED who were given a daily 4-mg dose of inositol plus 400 lg of FA or placebo in three doses.…”

Erectile dysfunction, diabetes and cardiovascular risk

“…40,41 A combination of folic acid and tadalafil has been shown to be more effective than tadalafil alone in restoring erectile function in diabetic patients. 42 Other strategies to improve the response to oral PDE5 inhibitors include addition of L-arginine or use of daily dosing of a combination of PDE5 inhibitors. 43 In addition to improving ED, PDE5 inhibitors may reduce cardiovascular risk through a range of effects.…”

Efficacy and safety of phosphodieterase-5 inhibitors for treatment of erectile dysfunction secondary to spinal cord injury: a systemic review and meta-analysis

“…8,9 Nitric oxide (NO) released by nonadrenergic-noncholinergic nerves in the penis has an important role in initiating and maintaining of the penile erection process. 10,11 NO diffuses to smooth where it augments the formation of cyclic guanosine monophosphate, which acts as a second messenger for engorgement of penile vasculature and penile erection. 12,13 Phosphodieterase-5 (PDE5) could facilitate the breakdown of cyclic guanosine monophosphate in the cavernosal smooth muscle where PDE5 is sufficient.…”