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Comparative efficacy and safety of phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a Bayesian network meta-analysis of randomized controlled trials

  • Xinyang Liao
  • Shi Qiu
  • Yige Bao
  • Wanyu Wang
  • Lu Yang
  • Qiang Wei
Review
  • 12 Downloads

Abstract

Purpose

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.

Results

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.

Conclusions

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.

Keywords

Erectile dysfunction Diabetes Phosphodiesterase type 5 inhibitors Network meta-analysis 

Supplementary material

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Supplementary material 1 (DOCX 73 kb)
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Supplementary material 2 (DOCX 27 kb)
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Supplementary material 3 (DOCX 514 kb)
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Supplementary material 4 (DOCX 302 kb)
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Supplementary material 5 (DOCX 28 kb)

References

  1. 1.
    NIH Consensus Conference Impotence (1993) NIH consensus development panel on impotence. JAMA 270(1):83–90.  https://doi.org/10.1001/jama.1993.03510010089036 CrossRefGoogle Scholar
  2. 2.
    Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB (1994) Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151(1):54–61.  https://doi.org/10.1016/S0022-5347(17)34871-1 CrossRefPubMedGoogle Scholar
  3. 3.
    Sasaki H, Yamasaki H, Ogawa K, Nanjo K, Kawamori R, Iwamoto Y, Katayama S, Shirai M (2005) Prevalence and risk factors for erectile dysfunction in Japanese diabetics. Diabet Res Clin Pract 70(1):81–89.  https://doi.org/10.1016/j.diabres.2005.02.018 (Epub 2005 Apr 15) CrossRefGoogle Scholar
  4. 4.
    Cho NH, Ahn CW, Park JY, Ahn TY, Lee HW, Park TS, Kim IJ, Pomerantz K, Park C, Kimm KC, Choi DS (2006) Prevalence of erectile dysfunction in Korean men with Type 2 diabetes mellitus. Diabet Med 23(2):198–203.  https://doi.org/10.1111/j.1464-5491.2005.01789.x CrossRefPubMedGoogle Scholar
  5. 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
  6. 6.
    Saigal CS, Wessells H, Pace J, Schonlau M, Wilt TJ (2006) Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med 166(2):207–212.  https://doi.org/10.1001/archinte.166.2.207 CrossRefPubMedGoogle Scholar
  7. 7.
    Sun P, Cameron A, Seftel A, Shabsigh R, Niederberger C, Guay A (2006) Erectile dysfunction—an observable marker of diabetes mellitus? A large national epidemiological study. J Urol 176(3):1081–1085.  https://doi.org/10.1016/j.juro.2006.04.082 (discussion 1085) CrossRefPubMedGoogle Scholar
  8. 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
  9. 9.
    Hecht MJ, Neundörfer B, Kiesewetter F, Hilz MJ (2001) Neuropathy is a major contributing factor to diabetic erectile dysfunction. Neurol Res 23(6):651–654.  https://doi.org/10.1179/016164101101198965 CrossRefPubMedGoogle Scholar
  10. 10.
    Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH (1992) Nitric oxide: a physiologic mediator of penile erection. Science 257(5068):401–403CrossRefPubMedGoogle Scholar
  11. 11.
    Hellstrom WJ, Monga M, Wang R, Domer FR, Kadowitz PJ, Roberts JA (1994) Penile erection in the primate: induction with nitric-oxide donors. J Urol 151(6):1723–1727.  https://doi.org/10.1016/s0022-5347(17)35353-3 CrossRefPubMedGoogle Scholar
  12. 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. 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
  14. 14.
    Lue TF (2000) Erectile dysfunction. N Engl J Med 342(24):1802–1813.  https://doi.org/10.1056/NEJM200006153422407 CrossRefPubMedGoogle Scholar
  15. 15.
    Fonseca V, Seftel A, Denne J, Fredlund P (2014) Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials. Diabetologia 47:1914–1923 [0012-186X (Print)] CrossRefGoogle Scholar
  16. 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
  17. 17.
    Burns PR, Rosen RC, Dunn M, Baygani SK, Perelman MA (2015) Treatment satisfaction of men and partners following switch from on-demand phosphodiesterase type 5 inhibitor therapy to tadalafil 5 mg once daily. J Sex Med 12(3):720–727.  https://doi.org/10.1111/jsm.12818 CrossRefPubMedGoogle Scholar
  18. 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. 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. 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
  21. 21.
    Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A (1997) The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49(6):822–830.  https://doi.org/10.1016/S0090-4295(97)00238-0 CrossRefPubMedGoogle Scholar
  22. 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. 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. 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
  25. 25.
    Salanti G, Ades AE, Ioannidis JPA (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64(2):163–171.  https://doi.org/10.1016/j.jclinepi.2010.03.016 CrossRefPubMedGoogle Scholar
  26. 26.
    van Valkenhoef G, Tervonen T, Zhao J, de Brock B, Hillege HL, Postmus D (2012) Multicriteria benefit-risk assessment using network meta-analysis. J Clin Epidemiol 65(4):394–403.  https://doi.org/10.1016/j.jclinepi.2011.09.005 CrossRefPubMedGoogle Scholar
  27. 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
  28. 28.
    Ziegler D, Merfort F, Van Ahlen H, Yassin A, Reblin T, Neureither M (2006) ED PHARMACOTHERAPY: efficacy and safety of flexible-dose vardenafil in men with type 1 diabetes and erectile dysfunction. J Sex Med 3(5):883–891CrossRefPubMedGoogle Scholar
  29. 29.
    Stuckey BG, Jadzinsky MN, Murphy LJ, Montorsi F, Kadioglu A, Fraige F, Manzano P, Deerochanawong C (2003) Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial. Diabetes Care 26(2):279–284CrossRefPubMedGoogle Scholar
  30. 30.
    Safarinejad MR (2004) Oral sildenafil in the treatment of erectile dysfunction in diabetic men: a randomized double-blind and placebo-controlled study. J Diabetes Complications 18(4):205–210.  https://doi.org/10.1016/S1056-8727(03)00056-4 CrossRefPubMedGoogle Scholar
  31. 31.
    Rendell MS, Rajfer J, Wicker PA, Smith MD (1999) Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial, Sildenafil Diabetes Study Group. JAMA 281(5):421–426CrossRefPubMedGoogle Scholar
  32. 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. 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
  34. 34.
    Moon DG, Yang DY, Lee CH, Ahn TY, Min KS, Park K, Park JK, Kim JJ (2011) A Therapeutic confirmatory study to assess the safety and efficacy of Zydena®(Udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus. J Sex Med 8(7):2048–2061CrossRefGoogle Scholar
  35. 35.
    Ishii N, Nagao K, Fujikawa K, Tachibana T, Iwamoto Y, Kamidono S (2006) Vardenafil 20-mg demonstrated superior efficacy to 10-mg in Japanese men with diabetes mellitus suffering from erectile dysfunction. Int J Urol 13(8):1066–1072CrossRefPubMedGoogle Scholar
  36. 36.
    Hatzichristou D, Gambla M, Rubio-Aurioles E, Buvat J, Brock GB, Spera G, Rose L, Lording D, Liang S (2008) Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction. Diabet Med 25(2):138–146.  https://doi.org/10.1111/j.1464-5491.2007.02338.x CrossRefPubMedGoogle Scholar
  37. 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
  38. 38.
    Escobar-Jimenez F, Grupo de Estuido Espanol sobre S (2002) Efficacy and safety of sildenafil in men with type 2 diabetes mellitus and erectile dysfunction. Med Clin (Barc) 119(4):121–124CrossRefGoogle Scholar
  39. 39.
    De Tejada IS, Anglin G, Knight JR, Emmick JT (2002) Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 25(12):2159–2164CrossRefGoogle Scholar
  40. 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
  41. 41.
    Boulton AJ, Selam JL, Sweeney M, Ziegler D (2001) Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus. Diabetologia 44(10):1296–1301.  https://doi.org/10.1007/s001250100656 CrossRefPubMedGoogle Scholar
  42. 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. 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. 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. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Urology, Institute of Urology, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  2. 2.Department of AnesthesiologyWest China Hospital of Sichuan UniversityChengduPeople’s Republic of China

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