Effects of sarpogrelate on microvascular complications with type 2 diabetes

  • Hyunju Yoo
  • Inwhee Park
  • Dae Jung Kim
  • Sukhyang LeeEmail author
Research Article


Background Diabetes is a major cause of microvascular complications. Renin–angiotensin–aldosterone blockers have been known to have the benefits of delaying onset and progression of diabetic complications including nephropathy. Objective To evaluate the effect of sarpogrelate, an antiplatelet agent, on the new onset diabetic complications in patients with type 2 diabetes mellitus. Setting A 1108-bed tertiary university hospital in Korea. Methods A retrospective cohort study was conducted using electronic medical records between 2010 and 2015 in Korea. The study cohort of the propensity score matched patients with or without sarpogrelate was evaluated for the diabetic complications identified with the diagnosis codes in T2DM patients on the metformin based antidiabetic therapy. Nephropathy was further evaluated for progression of kidney function. Main outcome measure The incidence of composite microvascular complications included nephropathy, neuropathy, and retinopathy. Results The 1:2 propensity score matched 478 out of 14,440 patients were included in the final analysis with or without sarpogrelate (162 vs. 316 patients). The incidence of nephropathy, neuropathy, and retinopathy was 1.23% versus 5.38% (HR 0.21, 95% CI 0.05–0.92), 1.23% versus 4.43% (HR 0.26, 95% CI 0.06–1.14), and 6.17% versus 6.33% (HR 0.93, 95% CI 0.43–1.97) with sarpogrelate and without sarpogrelate, respectively. Changes in the estimated glomerular filtration rate and urine albumin creatinine ratio were not significantly different between the groups. Conclusion In Korean patients, sarpogrelate, an antiplatelet agent, was associated with reducing the incidence and progression of nephropathyin type 2 diabetes, but not associated with the composite endpoints including neuropathy and retinopathy.


Diabetic complications Nephropathy Neuropathy Retinopathy Sarpogrelate Korea 



This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation, funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (No. 2013M3A9B5075838).

Conflicts of interest

The authors have no conflicts of interest which are directly relevant to the content of this study.

Supplementary material

11096_2019_794_MOESM1_ESM.docx (60 kb)
Supplementary material 1 (DOCX 59 kb)


  1. 1.
    Cho N, Shaw J, Karuranga S, Huang Y, da Rocha Fernandes J, Ohlrogge A, et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.CrossRefGoogle Scholar
  2. 2.
    Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–53.CrossRefGoogle Scholar
  3. 3.
    American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S86–104.CrossRefGoogle Scholar
  4. 4.
    Young BA, Lin E, Von Korff M, Simon G, Ciechanowski P, Ludman EJ, et al. Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care. 2008;14:15–23.Google Scholar
  5. 5.
    Hex N, Bartlett C, Wright D, Taylor M, Varley D. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabetic Med. 2012;29:855–62.CrossRefGoogle Scholar
  6. 6.
    Yoon J, Oh I, Seo H, Kim E, Gong Y, Ock M, et al. Disability-adjusted life years for 313 diseases and injuries: the 2012 Korean burden of disease study. J Korean Med Sci. 2016;31:S146–57.CrossRefGoogle Scholar
  7. 7.
    Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93:137–88.CrossRefGoogle Scholar
  8. 8.
    American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S105–18.CrossRefGoogle Scholar
  9. 9.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet. 1998;352:837–53.CrossRefGoogle Scholar
  10. 10.
    Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.CrossRefGoogle Scholar
  11. 11.
    Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. The Lancet. 2010;376:419–30.CrossRefGoogle Scholar
  12. 12.
    ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.CrossRefGoogle Scholar
  13. 13.
    Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.CrossRefGoogle Scholar
  14. 14.
    Neal B, Perkovic V, Mahaffey KW, De Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–57.CrossRefGoogle Scholar
  15. 15.
    Mann JF, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377:839–48.CrossRefGoogle Scholar
  16. 16.
    Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.CrossRefGoogle Scholar
  17. 17.
    Katayama S, Yamada D, Nakayama M, Yamada T, Myoishi M, Kato M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy. J Diabetes Complicat. 2017;31:758–65.CrossRefGoogle Scholar
  18. 18.
    Lee D, Chun EJ, Hur JH, Min SH, Lee J, Oh TJ, et al. Effect of sarpogrelate, a selective 5-HT 2A receptor antagonist, on characteristics of coronary artery disease in patients with type 2 diabetes. Atherosclerosis. 2017;257:47–54.CrossRefGoogle Scholar
  19. 19.
    Takahashi T, Yano M, Minami J, Haraguchi T, Koga N, Higashi K, et al. Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy. Diabetes Res Clin Pract. 2002;58:123–9.CrossRefGoogle Scholar
  20. 20.
    Hamasaki Y, Doi K, Maeda-Mamiya R, Ogasawara E, Katagiri D, Tanaka T, et al. A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal tubulointerstitial fibrosis by suppressing PAI-1. Am J Physiol Renal Physiol. 2013;305:F1796–803.CrossRefGoogle Scholar
  21. 21.
    Lee ES, Lee MY, Kwon M, Kim HM, Kang JS, Kim YM, et al. Sarpogrelate hydrochloride ameliorates diabetic nephropathy associated with inhibition of macrophage activity and inflammatory reaction in db/db mice. PLoS ONE. 2017;12:e0179221.CrossRefGoogle Scholar
  22. 22.
    Rosansky SJ, Glassock RJ. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials? Kidney Int. 2014;85:723–7.CrossRefGoogle Scholar
  23. 23.
    Stevens LA, Greene T, Levey AS. Surrogate end points for clinical trials of kidney disease progression. Clin J Am Soc Nephrol. 2006;1:874–84.CrossRefGoogle Scholar
  24. 24.
    Schmieder RE, Mann JF, Schumacher H, Gao P, Mancia G, Weber MA, et al. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol. 2011;22:1353–64.CrossRefGoogle Scholar
  25. 25.
    Investigators Gusto. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673–82.CrossRefGoogle Scholar
  26. 26.
    American Diabetes Association. 6. Glycemic targets: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S55–64.CrossRefGoogle Scholar
  27. 27.
    Kleinbaum DG, Klein M. Survival analysis. Berlin: Springer; 2010.Google Scholar
  28. 28.
    Lin D, Wei L, Ying Z. Model-checking techniques based on cumulative residuals. Biometrics. 2002;58:1–12.CrossRefGoogle Scholar
  29. 29.
    Anonymous Standards of Medical Care in Diabetes-2018. Diabetes Care January 01 2018;41:s1.Google Scholar
  30. 30.
    de Boer IH, Afkarian M, Rue TC, Cleary PA, Lachin JM, Molitch ME, et al. Renal outcomes in patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol. 2014;25:2342–50.CrossRefGoogle Scholar
  31. 31.
    Bailey RA, Wang Y, Zhu V, Rupnow MF. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7:415.CrossRefGoogle Scholar
  32. 32.
    Chu Y, Lin H, Wang J, Weng S, Lin C, Chien C. Epidemiology and outcomes of hypoglycemia in patients with advanced diabetic kidney disease on dialysis: a national cohort study. PLoS ONE. 2017;12:e0174601.CrossRefGoogle Scholar
  33. 33.
    Song SO, Lee Y, Kim DW, Song YD, Nam JY, Park KH, et al. Trends in diabetes incidence in the last decade based on Korean National Health Insurance claims data. Endocrinol Metab. 2016;31:292–9.CrossRefGoogle Scholar
  34. 34.
    Ko SH, Kim DJ, Park JH, et al. Trends of antidiabetic drug use in adult type 2 diabetes in Korea in 2002–2013: nationwide population-based cohort study. Medicine. 2016;95:e4018.CrossRefGoogle Scholar
  35. 35.
    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving H, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.CrossRefGoogle Scholar
  36. 36.
    Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, et al. Angiotensin-receptor blockade versus converting–enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351:1952–61.CrossRefGoogle Scholar
  37. 37.
    Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. The Lancet. 2000;355:253–9.CrossRefGoogle Scholar
  38. 38.
    National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60:850–86.CrossRefGoogle Scholar
  39. 39.
    Haluzik M, Frolik J, Rychlik I. Renal effects of DPP-4 inhibitors: a focus on microalbuminuria. Int J Endocrinol. 2013;2013:895102.CrossRefGoogle Scholar
  40. 40.
    Rathmann W, Kostev K, Gruenberger J, Dworak M, Bader G, Giani G. Treatment persistence, hypoglycaemia and clinical outcomes in type 2 diabetes patients with dipeptidyl peptidase-4 inhibitors and sulphonylureas: a primary care database analysis. Diabetes Obes Metab. 2013;15:55–61.CrossRefGoogle Scholar
  41. 41.
    Tanaka T, Higashijima Y, Wada T, Nangaku M. The potential for renoprotection with incretin-based drugs. Kidney Int. 2014;86:701–11.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Clinical Pharmacy, College of PharmacyAjou UniversitySuwonRepublic of Korea
  2. 2.Department of Nephrology, College of MedicineAjou UniversitySuwonRepublic of Korea
  3. 3.Department of Endocrinology, College of MedicineAjou UniversitySuwonRepublic of Korea

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