Comparative efficacy and safety of phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a Bayesian network meta-analysis of randomized controlled trials
- 122 Downloads
To compare the efficacy and safety profiles of different phosphodiesterase-5 inhibitors (PDE5Is) administrations for erectile dysfunction (ED) in diabetic men, including on-demand (PRN) and regular regimens (OAD).
Materials and methods
Searches were carried out in four electronic databases: PubMed (until April 17th, 2017); Scopus (until April 17th, 2017); Embase (until April 17th, 2017); and Cochrane (until April 18th, 2017). The outcomes for this study are as follows: (1) Global Assessment Question (GAQ) positive response rate; (2) changes from baseline to the end of the study in Erectile Function Domain of International Index of Erectile Function (IIEF-EF); and (3) treatment-related adverse events (TRAEs). The comparative effects of PDE5I regimens were analyzed with random-effect models in a Bayesian Framework using the GeMTC R package.
We identified 1056 records, of which 15 randomized trials with 5274 patients were included. The included studies covered eight kinds of PDE5I administration: avanafil PRN; mirodenafil PRN; sildenafil PRN; tadalafil PRN; tadalafil OAD; udenafil PRN; udenafil OAD; vardenafil PRN; and placebo. In surface under the cumulative ranking curve analysis, vardenafil PRN ranked first, third and first, and mirodenafil PRN ranked second, first and second in GAQ, IIEF-EF, and TRAEs, respectively.
PDE5I administrations were generally efficient and well-tolerated in diabetic men. Among these administrations, vardenafil PRN and mirodenafil PRN seem to have a possible advantage of efficacy and avoiding adverse effects compared to others. There is no significant difference between regular and on-demand regimens of PDE5Is.
KeywordsErectile dysfunction Diabetes Phosphodiesterase type 5 inhibitors Network meta-analysis
- 5.Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, DeCarolis E, Zoccoli J, Defoy I (2006) The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease. Arch Intern Med 166(2):213–219. https://doi.org/10.1001/archinte.166.2.213 CrossRefPubMedGoogle Scholar
- 8.Malavige LS, Jayaratne SD, Kathriarachchi ST, Sivayogan S, Fernando DJ, Levy JC (2008) Erectile dysfunction among men with diabetes is strongly associated with premature ejaculation and reduced libido. J Sex Med 5(9):2125–2134. https://doi.org/10.1111/j.1743-6109.2008.00907.x CrossRefPubMedGoogle Scholar
- 12.Tessari P, Cecchet D, Cosma A, Vettore M, Coracina A, Millioni R, Iori E, Puricelli L, Avogaro A, Vedovato M (2010) Nitric oxide synthesis is reduced in subjects with type 2 diabetes and nephropathy. Diabetes 59(9):2152–2159. https://doi.org/10.2337/db09-1772 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Hatzimouratidis K, Giuliano F, Moncada I, Muneer A, Salonia A, Verze P (2017) EAU guidelines on erectile dysfunction, premature ejaculation, penile curvature and priapism. Available at http://uroweb.org/guideline/male-sexual-dysfunction/. Accessed 20 Mar 2017
- 16.Porst H, Giuliano F, Glina S, Ralph D, Casabé AR, Elion-Mboussa A, Shen W, Whitaker JS (2006) Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5 mg and 10 mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, Placebo-Controlled Trial. Eur Urol 50(2):351–359. https://doi.org/10.1016/j.eururo.2006.02.052 CrossRefPubMedGoogle Scholar
- 18.Behr-Roussel D, Gorny D, Mevel K, Caisey S, Bernabé J, Burgess G, Wayman C, Alexandre L, Giuliano F (2005) Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. Eur Urol 47(1):87–91. https://doi.org/10.1016/j.eururo.2004.09.005 CrossRefPubMedGoogle Scholar
- 19.Vignozzi L, Filippi S, Morelli A, Ambrosini S, Luconi M, Vannelli GB, Donati S, Crescioli C, Zhang X-H, Mirone V, Forti G, Maggi M (2006) Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. 3(3):419–431. https://doi.org/10.1111/j.1743-6109.2006.00208.x CrossRefGoogle Scholar
- 20.Brock G, Ni X, Oelke M, Mulhall J, Rosenberg M, Seftel A, D’Souza D, Barry J (2016) Efficacy of continuous dosing of tadalafil once daily vs tadalafil on demand in clinical subgroups of men with erectile dysfunction: a descriptive comparison using the integrated tadalafil databases. J Sex Med 13(5):860–875. https://doi.org/10.1016/j.jsxm.2016.02.171 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Higgins JPT, Green S (2010) Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. March 2011. https://handbook-5-1.cochrane.org. Accessed 4 Mar 2017
- 23.Puhan MA, Schünemann HJ, Murad MH, Li T, Brignardello-Petersen R, Singh JA, Kessels AG, Guyatt GH, Group GW (2014) A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ 349(sep24 5):g5630–g5630. https://doi.org/10.1136/bmj.g5630 CrossRefGoogle Scholar
- 24.van Valkenhoef G, Kuiper J (2016) Gemtc: Network meta-analysis using Bayesian methods. Available at https://cran.r-project.org/web/packages/gemtc/index.html. Accessed 14 Mar 2017
- 27.Goldstein I, Jones LA, Belkoff LH, Karlin GS, Bowden CH, Peterson CA, Trask BA, Day WW (2012) Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus. Elsevier, New York, pp 843–852Google Scholar
- 32.Park SH, Park SW, Cha BY, Park IB, Min KW, Sung YA, Kim TH, Lee JM, Park KS (2015) Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction. Asian J Androl 17(1):143–148. https://doi.org/10.4103/1008-682X.135983 CrossRefPubMedGoogle Scholar
- 33.Park HJ, Choi HK, Ahn TY, Park JK, Chung WS, Lee SW, Kim SW, Hyun JS, Park NC (2010) Efficacy and safety of oral mirodenafil in the treatment of erectile dysfunction in diabetic men in Korea: a multicenter, randomized, double-blind, placebo-controlled clinical trial. J Sex Med 7(8):2842–2850. https://doi.org/10.1111/j.1743-6109.2010.01888.x CrossRefPubMedGoogle Scholar
- 37.Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T, Taylor T (2003) Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diabetes Care 26(3):777–783CrossRefPubMedGoogle Scholar
- 40.Buvat J, Van Ahlen H, Schmitt H, Chan M, Kuepfer C, Varanese L (2006) Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: Scheduled use vs. on demand regimen evaluation (SURE) study in 14 European countries. J Sex Med 3(3):512–520CrossRefPubMedGoogle Scholar
- 42.Yuan J, Zhang R, Yang Z, Lee J, Liu Y, Tian J, Qin X, Ren Z, Ding H, Chen Q, Mao C, Tang J (2013) Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for erectile dysfunction: a systematic review and network meta-analysis. Eur Urol 63(5):902–912. https://doi.org/10.1016/j.eururo.2013.01.012 CrossRefPubMedGoogle Scholar
- 43.van Ahlen H, Wahle K, Kupper W, Yassin A, Reblin T, Neureither M (2005) Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in patients with erectile dysfunction and arterial hypertension treated with multiple antihypertensives. J Sex Med 2(6):856–864. https://doi.org/10.1111/j.1743-6109.2005.00150.x CrossRefPubMedGoogle Scholar
- 44.Fava M, Nurnberg HG, Seidman SN, Holloway W, Nicholas S, Tseng LJ, Stecher VJ (2006) Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 67(2):240–246CrossRefPubMedGoogle Scholar
- 45.Balhara YPS, Sarkar S, Gupta R (2015) Phosphodiesterase-5 inhibitors for erectile dysfunction in patients with diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Ind J Endocrinol Metab 19(4):451–461. https://doi.org/10.4103/2230-8210.159023 CrossRefGoogle Scholar