Top

Advances in Therapy

Published in:

Open Access 01-03-2021 | Peripheral Arterial Disease | Original Research

Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis

Authors: Angelo A. Bignamini, Ahmed Chebil, Giovanni Gambaro, Jiří Matuška

Published in: Advances in Therapy | Issue 3/2021

Abstract

Introduction

Micro- and macrovascular complications of diabetes are leading morbidities in the world population. They are responsible not only for increased mortality but also severe disabilities, which jeopardize quality of life (e.g., blindness, walking limitations, and renal failure requiring dialysis). The new antidiabetic agents (e.g., glucagon-like peptide 1 receptor agonists and sodium–glucose cotransporter inhibitors) are increasingly recognized as breakthrough agents in the treatment of diabetes and prevention of diabetic complications. However, drugs effective in preventing and treating diabetic disabilities are still needed and sulodexide could be one of those able to address the unmet clinical needs of the new antidiabetic agents.

Methods

We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings, and journal supplements. Any study monitoring any effect of sulodexide in subjects with diabetes, in relation to renal, vascular, and ocular complication, was considered. Treatment effects were estimated using standardized mean differences (SMDs), mean differences (MDs), and risk ratios (RRs), as appropriate. We calculated 95% confidence interval (CIs) and heterogeneity (Q, tau, and I²).

Results

The search found 45 studies with 2817 participants (mean age 57 years; 63% male). The 26 randomized controlled studies included 2074 participants (mean age 58.8 years; 66% male). Sulodexide reduced the impact of diabetic retinopathy; increased the pain-free and maximal walking distance in peripheral arterial disease; accelerated the healing of diabetes-associated trophic ulcers; and decreased the rate of albumin excretion in subjects with nephropathy. The risk of adverse events (AEs) was not different between sulodexide and controls.

Conclusion

Sulodexide has a beneficial effect on the ocular, peripheral arterial disease, trophic ulcers, and renal complications of diabetes without increasing the risk of AEs.

Available only for authorised users

DeFronzo RA, Ferrannini E, Zimmet P, Alberti KGMM. International textbook of diabetes mellitus. 4th ed. Hoboken: Wiley-Blackwell; 2015.CrossRef

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387(10027):1513–30. https://doi.org/10.1016/S0140-6736(16)00618-8.CrossRef

International Diabetes Federation. IDF Diabetes Atlas, 8th edition 2017. http://www.diabetesatlas.org. Accessed 9 Apr 2020.

GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858. https://doi.org/10.1016/S0140-6736(18)32279-7.CrossRef

Hewitt J, Castilla Guerra L, Fernández-Moreno MC, Sierra C. Diabetes and stroke prevention: a review. Stroke Res Treat. 2012;2012:673187. https://doi.org/10.1155/2012/673187.CrossRefPubMedPubMedCentral

Thiruvoipati T, Kielhorn CE, Armstrong EJ. Peripheral artery disease in patients with diabetes: epidemiology, mechanisms, and outcomes. World J Diabetes. 2015;6(7):961–9. https://doi.org/10.4239/wjd.v6.i7.961.CrossRefPubMedPubMedCentral

Zoungas S, Arima H, Gerstein HC, et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol. 2017;5(6):431–7. https://doi.org/10.1016/S2213-8587(17)30104-3.CrossRefPubMed

Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91. https://doi.org/10.1056/NEJMoa0706245.CrossRefPubMed

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57. https://doi.org/10.1056/NEJMoa1611925.CrossRefPubMed

10.

Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32(4):219–26. https://doi.org/10.1007/BF00285287.CrossRefPubMed

11.

Dogné S, Flamion B, Caron N. Endothelial glycocalyx as a shield against diabetic vascular complications: involvement of hyaluronan and hyaluronidases. Arterioscler Thromb Vasc Biol. 2018;38(7):1427–39. https://doi.org/10.1161/ATVBAHA.118.310839.CrossRefPubMedPubMedCentral

12.

Abaterusso C, Gambaro G. The role of glycosaminoglycans and sulodexide in the treatment of diabetic nephropathy. Treat Endocrinol. 2006;5(4):211–22. https://doi.org/10.2165/00024677-200605040-00002.CrossRefPubMed

13.

Weiss R, Niecestro R, Raz I. The role of sulodexide in the treatment of diabetic nephropathy. Drugs. 2007;67(18):2681–96. https://doi.org/10.2165/00003495-200767180-00004.CrossRefPubMed

14.

Lewis EJ, Xu X. Abnormal glomerular permeability characteristics in diabetic nephropathy: implications for the therapeutic use of low-molecular weight heparin. Diabetes Care. 2008;31(Suppl 2):S202–7. https://doi.org/10.2337/dc08-s251.CrossRefPubMed

15.

Masola V, Zaza G, Gambaro G. Sulodexide and glycosaminoglycans in the progression of renal disease. Nephrol Dial Transplant. 2014;29(Suppl 1):i74–9. https://doi.org/10.1093/ndt/gft389.CrossRefPubMed

16.

Masola V, Zaza G, Onisto M, Lupo A, Gambaro G. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects. Int Angiol. 2014;33(3):243–54.PubMed

17.

Carroll BJ, Piazza G, Goldhaber SZ. Sulodexide in venous disease. J Thromb Haemost. 2019;17(1):31–8. https://doi.org/10.1111/jth.14324.CrossRefPubMed

18.

Coccheri S, Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Dev Ther. 2013;8:49–65. https://doi.org/10.2147/DDDT.S6762.CrossRef

19.

Yung S, Chau MK, Zhang Q, Zhang CZ, Chan TM. Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy. PLoS One. 2013;8(1):e54501. https://doi.org/10.1371/journal.pone.0054501.CrossRefPubMedPubMedCentral

20.

Roshan-Milani S, Khalilpour J, Abdollahzade FA. The heparanase inhibitor (sulodexide) decreases urine glycosaminoglycan excretion and mitigates functional and histological renal damages in diabetic rats. Acta Med Bulg. 2019;46(2):41–6. https://doi.org/10.2478/amb-2019-0017.CrossRef

21.

Gambaro G, Cavazzana AO, Luzi P, et al. Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney Int. 1992;42(2):285–91. https://doi.org/10.1038/ki.1992.288.CrossRefPubMed

22.

Gambaro G, Venturini AP, Noonan DM, et al. Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy. Kidney Int. 1994;46(3):797–806. https://doi.org/10.1038/ki.1994.335.CrossRefPubMed

23.

Kristová V, Lísková S, Sotníková R, Vojtko R, Kurtanský A. Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res. 2008;57(3):491–4.PubMed

24.

Li T, Liu X, Zhao Z, Ni L, Liu C. Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury rat carotid artery model. Oncotarget. 2017;8(53):91350–61. https://doi.org/10.18632/oncotarget.20518.CrossRefPubMedPubMedCentral

25.

Liu YN, Zhou J, Li T, et al. Sulodexide protects renal tubular epithelial cells from oxidative stress-induced injury via upregulating klotho expression at an early stage of diabetic kidney disease. J Diabetes Res. 2017;2017:4989847. https://doi.org/10.1155/2017/4989847.CrossRefPubMedPubMedCentral

26.

Song JW, Zullo JA, Liveris D, Dragovich M, Zhang XF, Goligorsky MS. Therapeutic restoration of endothelial glycocalyx in sepsis. J Pharmacol Exp Ther. 2017;361(1):115–21. https://doi.org/10.1124/jpet.116.239509.CrossRefPubMedPubMedCentral

27.

Li T, Liu C. Sulodexide recovers endothelial function through reconstructing glycocalyx in the balloon-injury rat carotid artery model. Int Angiol. 2018;37:72.

28.

Broekhuizen LN, Lemkes BA, Mooij HL, et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010;53(12):2646–55. https://doi.org/10.1007/s00125-010-1910-x.CrossRefPubMedPubMedCentral

29.

Mannello F, Ligi D, Raffetto JD. Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease. Int Angiol. 2014;33(3):236–42.PubMed

30.

Mannello F, Ligi D, Canale M, Raffetto JD. Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors from human macrophages: role of glycosaminoglycans in inflammatory pathways of chronic venous disease. Curr Vasc Pharmacol. 2014;12(1):173–85. https://doi.org/10.2174/1570161111666131126144025.CrossRefPubMed

31.

Ligi D, Mosti G, Croce L, Raffetto JD, Mannello F. Chronic venous disease—part I: inflammatory biomarkers in wound healing. Biochim Biophys Acta. 2016;1862(10):1964–74. https://doi.org/10.1016/j.bbadis.2016.07.018.CrossRefPubMed

32.

Ligi D, Mosti G, Croce L, Raffetto JD, Mannello F. Chronic venous disease—part II: proteolytic biomarkers in wound healing. Biochim Biophys Acta. 2016;1862(10):1900–8. https://doi.org/10.1016/j.bbadis.2016.07.011.CrossRefPubMed

33.

Ligi D, Benitez S, Croce L, et al. Electronegative LDL induces MMP-9 and TIMP-1 release in monocytes through CD14 activation: inhibitory effect of glycosaminoglycan sulodexide. Biochim Biophys Acta Mol Basis Dis. 2018;1864(12):3559–67. https://doi.org/10.1016/j.bbadis.2018.09.022.CrossRefPubMed

34.

Shu J, Zeng LY, Lin KY, et al. Renal protective effects of sulodexide in diabetic rats and its anti-oxidative mechanism. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(4):778–80.PubMed

35.

Gabryel B, Jarząbek K, Machnik G, et al. Superoxide dismutase 1 and glutathione peroxidase 1 are involved in the protective effect of sulodexide on vascular endothelial cells exposed to oxygen-glucose deprivation. Microvasc Res. 2016;103:26–35. https://doi.org/10.1016/j.mvr.2015.10.001.CrossRefPubMed

36.

De Felice F, Megiorni F, Pietrantoni I, et al. Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program. Eur Rev Med Pharmacol Sci. 2019;23(6):2669–80. https://doi.org/10.26355/eurrev_201903_17415.CrossRefPubMed

37.

Masola V, Onisto M, Zaza G, Lupo A, Gambaro G. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J Transl Med. 2012;10:213. https://doi.org/10.1186/1479-5876-10-213.CrossRefPubMedPubMedCentral

38.

Xu G, Qin Q, Yang M, Qiao Z, Gu Y, Niu J. Heparanase-driven inflammation from the AGEs-stimulated macrophages changes the functions of glomerular endothelial cells. Diabetes Res Clin Pract. 2017;124:30–40. https://doi.org/10.1016/j.diabres.2016.12.016.CrossRefPubMed

39.

Giurdanella G, Lazzara F, Caporarello N, et al. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE. Biochem Pharmacol. 2017;142:145–54. https://doi.org/10.1016/j.bcp.2017.06.130.CrossRefPubMed

40.

Matuska J, Benova K. Development of wall stiffness parameters in diabetes mellitus type II—evaluation of therapeutic effect of sulodexide vs naftidrofuryl: an open controlled 2-year study. Vasa-Eur J Vasc Med. 2017;46:30. https://doi.org/10.1024/0301-1526/a000651.CrossRef

41.

Cha JJ, Kang YS, Hyun YY, et al. Sulodexide improves renal function through reduction of vascular endothelial growth factor in type 2 diabetic rats. Life Sci. 2013;92(23):1118–24. https://doi.org/10.1016/j.lfs.2013.04.008.CrossRefPubMed

42.

Tiurenkov IN, Voronkov AV, Slietsans AA, Snigur GL. Effects of mexidol and sulodexide on the level of specific markers of endothelial dysfunction in animals with experimental diabetes mellitus. Eksp Klin Farmakol. 2012;75(5):14–6.PubMed

43.

Raffetto JD, Calanni F, Mattana P, Khalil RA. Sulodexide promotes arterial relaxation via endothelium-dependent nitric oxide-mediated pathway. Biochem Pharmacol. 2019;166:347–56. https://doi.org/10.1016/j.bcp.2019.04.021.CrossRefPubMedPubMedCentral

44.

Condorelli M, Chiariello M, Dagianti A, et al. IPO-V2: a prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction. J Am Coll Cardiol. 1994;23(1):27–34. https://doi.org/10.1016/0735-1097(94)90498-7.CrossRefPubMed

45.

Peterkova V, Mishina I, Sherbacheva L. Sulodexide in the treatment of diabetic nephropathy in children. Diabetes (Mosk). 1999;3:31–3.

46.

Higgins JP, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions, version 6.0. New York: Wiley; 2019.CrossRef

47.

Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. https://doi.org/10.1136/bmj.l4898.CrossRefPubMed

48.

Balduzzi S, Rucker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019;22(4):153–60. https://doi.org/10.1136/ebmental-2019-300117.CrossRefPubMed

49.

R Core Team. A language and environment for statistical computing. 2015. R foundation for statistical computation, Vienna, Austria. https://www.R-project.org/. Accessed 17 Mar 2020.

50.

Higgins JP, Li T, Deeks JJ, et al. Choosing effect measures and computing estimates of effect, version 6.0. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al., editors. Cochrane handbook for systematic reviews of interventions. New York: Wiley; 2019. p. 143–76.CrossRef

51.

Lipsey MW, Wilson DB. Practical meta-analysis. Thousand Oaks: SAGE; 2001.

52.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. https://doi.org/10.1186/1471-2288-14-135.CrossRefPubMedPubMedCentral

53.

Chen S, Wei M, Gao Y, et al. A randomized controlled trial of sulodexide for early diabetic nephropathy. Chin J Evid Based Med. 2008;8(3):162–6. https://doi.org/10.7507/1672-2531.20080037.CrossRef

54.

Hu M, Lv B, Meng Y, Zhou J, Xu X, Xiao X. Therapeutic effects of sulodexide combined with irbesartan on elderly patients with diabetic nephropathy. Pract Geriatr. 2009;23(4):276–8.

55.

Wang T-J, Wang Z-S, Yang F. Clinical observation of sulodexide in treatment of type 2 diabetes with early nephropathy. Med Pharm World. 2009;11:769–71.

56.

Hu M, Lv B, Meng Y, Zhou J, Xu X, Xiao X. Therapeutic effects of perindopril combined with sulodexide on elderly early patients with diabetic nephropathy. Southwest Nat Defence Med. 2010;20:501–3.

57.

Liu S. Therapeutic effects of sulodexide combined with benazapril on patients with diabetic kidney disease. Chin J Diffic Compl Cas. 2011;10:21–2.

58.

Ma J, Jiang H, Cui Q, Song B. Clinical observation of sulodexide in reducing microalbumi-nuria in diabetic nephropathy patients. Mod Prev Med. 2011;38:2918–9.

59.

Zhang H, Kang P, Li J, et al. Study of the effect of Chulo on albuminuria in diabetic nephropathy. Med J Integr Tradit Chin West Med. 2011;20:405–6.

60.

Huo S, Huang M, Liu Y. Clinical observation of sulodexide in treatment of in reducing proteinuria in type 2 diabetic nephropathy patients. Hebei Med J. 2014;36:191–2.

61.

Chen L, Yang R. Effect of sulodexide on urine protein excretion in type 2 diabetes with proteinuria. Med J Wuhan Univ. 2015;34:450–2.

62.

Rubbi F, Caramazza R, Boccia S, et al. The effects of sulodexide on diabetic retinopathy. Minerva Cardioangiol. 2000;48(Suppl 1):81–2.

63.

Shadrichev F. The effect of diabetic nephropathy therapy with “Vessel Due F” (sulodexide) on the risk of intraocular hemorrhages in patients with proliferative diabetic retinopathy. Ophthalmol Gazette. 2009;2(2):49–53.

64.

Song JH, Chin HS, Kwon OW, Lim SJ, Kim HK, DRESS Research Group. Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS). Graefes Arch Clin Exp Ophthalmol. 2015;253(6):829–37. https://doi.org/10.1007/s00417-014-2746-8.CrossRefPubMed

65.

Belcaro G, Dugall M, Bradford HD, et al. Recurrent retinal vein thrombosis: prevention with aspirin, Pycnogenol®, ticlopidine, or sulodexide. Minerva Cardioangiol. 2019;67(2):109–14. https://doi.org/10.23736/S0026-4725.19.04891-6.CrossRefPubMed

66.

Utratová J, Mayer J, Elbl L, Vorlícek J, Prásek J. Experience with sulodexide (Vessel Due F) in diabetics with ischemic disease of the lower extremities. Vnitr Lek. 1993;39(6):575–80.PubMed

67.

Bregovsky V, Zalesskaya A. The use of sulodexide in obliterating atherosclerosis of the lower extremities in patients with diabetes mellitus. Prob Endocrinol. 1998;44(4):16–8.CrossRef

68.

Koblik T, Sieradzki J, Sendur R, et al. The effect of insulin and sulodexide (Vessel Due F) on diabetic foot syndrome: pilot study in elderly patients. J Diabetes Complicat. 2001;15(2):69–74. https://doi.org/10.1016/s1056-8727(00)00134-3.CrossRef

69.

Coccheri S, Scondotto G, Agnelli G, Palazzini E, Zamboni V, Arterial Arm of the Suavis (Sulodexide Arterial Venous Italian Study) Group. Sulodexide in the treatment of intermittent claudication. Results of a randomized, double-blind, multicentre, placebo-controlled study. Eur Heart J. 2002;23(13):1057–65. https://doi.org/10.1053/euhj.2001.3033.CrossRefPubMed

70.

Moldovan C, Marc F, Farcaş D. Sulodexide treatment in patients with type 2 diabetes mellitus and intermittent claudication. Eur J Int Med. 2011;22:S63.CrossRef

71.

Katorkin SE. Significance of endothelial protection in treatment of patients with class c6 chronic venous disease and type 2 diabetes mellitus. Angiol Sosud Khir. 2015;21(3):99–102 (104–6).PubMed

72.

Zakharova NO, Bulgakova SV, Katorkin SE, Melnikov MA, Treneva EV, Nikolaeva AV. The treatment of elderly and senile patients with venous trophic ulcers and type 2 diabetes mellitus. Adv Gerontol. 2017;30(6):917–24.PubMed

73.

Solini A, Carraro A, Barzon I, Crepaldi G. Therapy with glycosaminoglycans lowers albumin excretion rate in non-insulin dependent diabetic patients with macroalbuminuria. Diabetes Nutr Metab. 1994;7(5):304–7.

74.

Velussi M, Cernigoi A, Dapas F, De Monte A. Glycosaminoglycans oral therapy reduces microalbuminuria, blood fibrinogen levels and limb arteriopathy clinical signs in patients with non-insulin dependent diabetes mellitus. Diabetes Nutr Metab. 1996;9(2):53–8.

75.

Dedov I, Shestakova M, Vorontzov A, Palazzini E. A randomized, controlled study of sulodexide therapy for the treatment of diabetic nephropathy. Nephrol Dial Transplant. 1997;12(11):2295–300. https://doi.org/10.1093/ndt/12.11.2295.CrossRefPubMed

76.

Perušičová J, Škrha J. The effect of sulodexide, a glycosaminoglycan, on albuminuria in diabetic patients. Vnitr Lek. 1997;43(11):748–52.PubMed

77.

Poplawska A, Szelachowska M, Topolska J, Wysocka-Solowie B, Kinalska I. Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria. Diabetes Res Clin Pract. 1997;38(2):109–14. https://doi.org/10.1016/s0168-8227(97)00096-x.CrossRefPubMed

78.

Shestakova MV, Chugunova LA, Vorontsov AV, Dedov II. The efficacy of sulodexide—a low-molecular heparin—in the therapy of diabetic nephropathy. Ter Arkh. 1997;69(6):34–7.PubMed

79.

Škrha J, Perušičová J, Pont’uch P, Okša A. Glycosaminoglycan sulodexide decreases albuminuria in diabetic patients. Diabetes Res Clin Pract. 1997;38(1):25–31. https://doi.org/10.1016/s0168-8227(97)00076-4.CrossRefPubMed

80.

Solini A, Vergnani L, Ricci F, Crepaldi G. Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care. 1997;20(5):819–23. https://doi.org/10.2337/diacare.20.5.819.CrossRefPubMed

81.

Sorrenti G, Grimaldi M, Canova N, Palazzini E, Melchionda N. Glycosaminoglycans as a possible tool for micro- and macroalbuminuria in diabetic patients. A pilot study. J Int Med Res. 1997;25(2):81–6. https://doi.org/10.1177/030006059702500204.CrossRefPubMed

82.

Szelachowska M, Poplawska A, Topolska J, Kinalska I, Grimaldi M. A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type I diabetic patients. Curr Med Res Opin. 1997;13(9):539–45. https://doi.org/10.1185/03007999709113327.CrossRefPubMed

83.

Rasovskiĭ BL, Tarasov AV, Trel’skaia N, Severina TI, Chernykh EF. Sulodexide in the treatment of diabetic nephropathy. Klin Med (Mosk). 1998;76(7):40–2.

84.

Škrha J, Perušičová J, Kvasnička J, Hilgertová J. The effect of glycosaminoglycan sulodexide on oxidative stress and fibrinolysis in diabetes mellitus. Sb Lek. 1998;99(2):103–9.PubMed

85.

Zalevskaia AG, Astamirova KhS, Karpova IA, Popova SG. A trial of the use of the low-molecular heparin sulodexide in the therapy of diabetic nephropathy. Ter Arkh. 1998;70(3):71–4.PubMed

86.

Oksa A, Pontuch P, Kratochvilova H. The effect of glycosaminoglycan sulodexide on albuminuria in patients with diabetes mellitus. Bratisl Lek Listy. 1999;100(9):486–9.PubMed

87.

Sun M, Tian L. Clinical study on type II diabetic nephropathy treated with sulodexide. Chi J Chin New Drugs J. 1999;8:408–10.

88.

Lichiardopol R, Ionescu-Tirgoviste C, Serban V, Dumitrescu C, Mota M, Ghise G. The effect of sulodexide on albuminuria in a group of patients with diabetes. Rom J Diabetes Nutr Metab Dis. 2001;2:28–31.

89.

Gambaro G, Kinalska I, Oksa A, et al. Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial. J Am Soc Nephrol. 2002;13(6):1615–25. https://doi.org/10.1097/01.asn.0000014254.87188.e5.CrossRefPubMed

90.

Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2005;18(5):568–74.PubMed

91.

Sulikowska B, Olejniczak H, Muszynska M, et al. Effect of sulodexide on albuminuria, NAG excretion and glomerular filtration response to dopamine in diabetic patients. Am J Nephrol. 2006;26(6):621–8. https://doi.org/10.1159/000098195.CrossRefPubMed

92.

Heerspink HL, Greene T, Lewis JB, et al. Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria. Nephrol Dial Transplant. 2008;23(6):1946–54. https://doi.org/10.1093/ndt/gfm893.CrossRefPubMed

93.

Blouza S, Dakhli S, Abid H, et al. Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2010;23(4):415–24.PubMed

94.

Mao L, Zhong X. Effect of sulodexide combined with benazepril on urinary albumin in patients with type 2 diabetes. Chin Mod Med. 2010;17:68–9.

95.

Jian R, Jie S, Can H. Effect of sulodexide on microalbuminuria of the third stage of type 2 diabetic nephropathy. Mod Med J Chin. 2010;11:20.

96.

Wang H. Effect of sulodexide in diabetic nephropathy. Prac J Med Pharm. 2010;27:315–6.

97.

Lewis EJ, Lewis JB, Greene T, et al. Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial. Am J Kidney Dis. 2011;58(5):729–36. https://doi.org/10.1053/j.ajkd.2011.06.020.CrossRefPubMed

98.

He X, Ge Z. Curative effect of sulodexide in diabetic nephropathy patients. Clin Foc. 2012;27:1626–7.

99.

Packham DK, Wolfe R, Reutens AT, et al. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J Am Soc Nephrol. 2012;23(1):123–30. https://doi.org/10.1681/ASN.2011040378.CrossRefPubMed

100.

Kang Z. Study on effect of sulodexide in treatment of diabetic nephropathy stage III. Guide Chin Med. 2013;11:25–8.

101.

Xiong Y. Treatment of sulodexide on albuminuria in early diabetic nephropathy. J Jianghan Univ (Nat Sci Ed). 2014;42(3):90–2.

102.

Satirapoj B, Kaewput W, Supasyndh O, Ruangkanchanasetr P. Effect of sulodexide on urinary biomarkers of kidney injury in normoalbuminuric type 2 diabetes: a randomized controlled trial. J Diabetes Res. 2015;2015:172038. https://doi.org/10.1155/2015/172038.CrossRefPubMedPubMedCentral

103.

Zilişteanu DS, Atasie T, Voiculescu M. Efficacy of long-term low-dose sulodexide in diabetic and non-diabetic nephropathies. Rom J Intern Med. 2015;53(2):161–9. https://doi.org/10.1515/rjim-2015-0022.CrossRefPubMed

104.

Dakhli S, Khedher A, Borni Z, Achour A, Hachicha J. A clinical experience on sulodexide in the treatment of patients with diabetic nephropathy. J Nephrol Ther. 2016;7(1):1000284. https://doi.org/10.4172/2161-0959.1000284.CrossRef

105.

Li H, Ke W, Liu J, He X Jr, Liu L, Li Y. Effect of intravenous and oral therapy with sulodexide on diabetic nephropathy. Diabetes. 2017;66:A597.

106.

Pisano L, Moronesi F, Falco F, et al. The use of sulodexide in the treatment of peripheral vasculopathy accompanying metabolic diseases. Controlled study in hyperlipidemic and diabetic subjects. Thromb Res. 1986;41(1):23–31. https://doi.org/10.1016/0049-3848(86)90276-8.CrossRefPubMed

107.

Piva I, Lora L, Baso A, Erle G. Controlled study of the effect of sulodexide on peripheral diabetic macroangiopathy. G Clin Med. 1985;66(1–2):37–45.PubMed

108.

Arsenio L, Strata A. Hyperlipidaemias in diabetes. Therapeutic effects of a parenterally administered glucosaminoglycan: sulodexide (Vessel Due). Clin Trials J. 1987;24:312–21.

109.

Szafilk J, Kamińska A. Usefulness of Vessel Due F (sulodexide) in treatment of patients with diabetic retinopathy, senile macular degeneration and retinal vein occlusion. Okulistyka. 2000;3:1–4.

110.

d’Aloia A, Dati M, Della Corte M, Romano M, Lanza M, Romano A. Assessment of the effectiveness of sulodexide on diabetic patients. Boll Oculistica. 2001;80(1):37–41.

111.

Karimov K, Shakhmaliyeva A. Effect of sulodexide on non-proliferative diabetic retinopathy. Azerbaijan Med J. 2002;1:72–6.

112.

Li R, Xing J, Mu X, et al. Sulodexide therapy for the treatment of diabetic nephropathy, a meta-analysis and literature review. Drug Des Devel Ther. 2015;9:6275–83. https://doi.org/10.2147/DDDT.S87973.CrossRefPubMedPubMedCentral

113.

Yan W, Zhou B, Shen Y, Xu G. Antioxidant and antithrombotic therapies for diabetic kidney disease. Iran J Kidney Dis. 2015;9(6):413–20.PubMed

114.

Lamblova K, Mlcoch T, Mazalova M, Dolezal T. Cost-effectiveness analysis of sulodexide in patients with non-proliferative diabetic retinopathy in the Czech Republic. Value Health. 2016;19(7):A568.CrossRef

115.

Tokmakova AY, Milenkaya T, Chirkova L, Arbuzova M, Antsiferov M. The use of the drug Wessel Duet F in the complex treatment of lesions of the lower extremities in patients with type II diabetes. Prob Endocrinol. 1999;45(3):14–8.CrossRef

116.

Klisarova A, Bihchelian H, Koeva L. Planary bone scintigraphy of the foot in the diabetics with peripheral macroangiopathy, treated with sulodexide (Vessel Due F). Rentgenol Radiol. 2000;39(4):281–4.

117.

Svetukhin AM, Zemlianoĭ AB, Orudzheva SA, et al. Experience in the use of vessel due F (sulodexide) in patients with suppurative-necrotic forms of diabetic foot without critical ischemia. Ter Arkh. 2001;73(4):31–3.PubMed

118.

Mozgovaya E, Pecherina L. Sulodexide efficacy in complex therapy and prevention of gestational toxicosis (gestosis) in patients with type 1 diabetes mellitus. Farmateka. 2006;3:128–33.

119.

Olde Engberink RH, Vogt L. The renoprotective effects of sulodexide. Drug Des Devel Ther. 2016;10:1233–4. https://doi.org/10.2147/DDDT.S102814.CrossRefPubMedPubMedCentral

120.

Shustov SB. Controlled clinical trial on the efficacy and safety of oral sulodexide in patients with peripheral occlusive arterial disease. Curr Med Res Opin. 1997;13(10):573–82. https://doi.org/10.1185/03007999709113331.CrossRefPubMed

121.

Apollonio A, Antignani PL, Di Salvo M, et al. A large Italian observational multicentre study on vascular ulcers of the lower limbs (Studio Ulcere Vascolari). Int Wound J. 2016;13(1):27–34. https://doi.org/10.1111/iwj.12216.CrossRefPubMed

122.

Arcangeli A, Pedone T, Crescenti C, Ianni L. Microalbuminuria and type-II diabetes: clinical efficacy of sulodexide. Preliminary data. Minerva Cardioangiol. 2000;48(11 Suppl 2):72–3.

123.

Piaggesi A, Abbruzzese L, Mattaliano C, et al. Sulodexide as adjunctive therapy in diabetic foot patients with critical limb ischemia treated with percutaneous transluminal angioplasty. Int J Low Extrem Wounds. 2014;13(2):103–9. https://doi.org/10.1177/1534734614534442.CrossRefPubMed

124.

Gohel MS, Taylor M, Earnshaw JJ, Heather BP, Poskitt KR, Whyman MR. Risk factors for delayed healing and recurrence of chronic venous leg ulcers–an analysis of 1324 legs. Eur J Vasc Endovasc Surg. 2005;29(1):74–7. https://doi.org/10.1016/j.ejvs.2004.10.002.CrossRefPubMed

125.

Coccheri S, Bignamini AA. Pharmacological adjuncts for chronic venous ulcer healing. Phlebology. 2016;31(5):366–7. https://doi.org/10.1177/0268355515619562.CrossRefPubMed

126.

Gambaro G. Discounting the efficacy of sulodexide in diabetic nephropathy is premature. Am J Kidney Dis. 2012;60(1):169–70. https://doi.org/10.1053/j.ajkd.2012.01.029.CrossRefPubMed

127.

Coccheri S. Game not over for sulodexide. Am J Kidney Dis. 2012;59(3):467.PubMedCrossRef

128.

Rozita M, Mohd Shahrir M, Loo C, et al. Glycosaminoglycans (sulodexide) for resistant heavy proteinuria of chronic glomerulonephritides. Nephrology. 2008;13(Suppl 1):A55.

129.

Kozlova L, Khokhlov R, Akhmedzhanov N. Clinical efficacy of glycosaminoglycans in patients with diabetes mellitus and ischemic heart disease. Rational Pharmacother Card. 2011;7(5):584–90.CrossRef

130.

Marcoux R, Larrat E, Taubman A, Wilson J. Screening for peripheral arterial disease. J Am Pharm Assoc (Wash). 1996;NS36:370–3.CrossRef

131.

Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006;114(7):688–99. https://doi.org/10.1161/CIRCULATIONAHA.105.593442.CrossRefPubMed

132.

Heerspink HJL, Greene T, Tighiouart H, et al. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019;7(2):128–39. https://doi.org/10.1016/S2213-8587(18)30314-0.CrossRefPubMed

133.

Inker LA, Heerspink HJL, Tighiouart H, et al. GFR slope as a surrogate end point for kidney disease progression in clinical trials: a meta-analysis of treatment effects of randomized controlled trials. J Am Soc Nephrol. 2019;30(9):1735–45. https://doi.org/10.1681/ASN.2019010007.CrossRefPubMedPubMedCentral

134.

Olde Engberink RH, Heerspink HJ, de Zeeuw D, Vogt L. Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies. Br J Clin Pharmacol. 2016;82(5):1351–7. https://doi.org/10.1111/bcp.13062.CrossRefPubMedPubMedCentral

135.

Bignamini AA, Matuška J. Sulodexide for the symptoms and signs of chronic venous disease: a systematic review and meta-analysis. Adv Ther. 2020;37(3):1013–33. https://doi.org/10.1007/s12325-020-01232-1.CrossRefPubMedPubMedCentral

136.

Gaddi A, Galetti C, Illuminati B, Nascetti S. Meta-analysis of some results of clinical trials on sulodexide therapy in peripheral occlusive arterial disease. J Int Med Res. 1996;24(5):389–406. https://doi.org/10.1177/030006059602400501.CrossRefPubMed

137.

Shang H-X, Zhao J-Y, Shen X, et al. The efficacy and safety of sulodexide in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2016;9(7):12481–91.

Title: Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis
Authors: Angelo A. Bignamini
Ahmed Chebil
Giovanni Gambaro
Jiří Matuška
Publication date: 01-03-2021
Publisher: Springer Healthcare
Keywords: Peripheral Arterial Disease
Peripheral Arterial Disease
Published in: Advances in Therapy / Issue 3/2021
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI: https://doi.org/10.1007/s12325-021-01620-1

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis

Abstract

Introduction

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2021

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis

Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data

A Prospective, Observational, Cohort Study to Assess the Efficacy and Safety of Prolonged-Release Fampridine in Cognition, Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients: The FAMILY Study

HCV Viral Load Greater Than 1000 IU/ml at Time of Virologic Failure in Direct-Acting Antiviral-Treated Patients

Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials

Extraperitoneal Laparoscopic Kidney Transplantation: Preliminary Clinical Experiences from China

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page