Effects of sarpogrelate on microvascular complications with type 2 diabetes

  • 211 Accesses

  • 1 Citations


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.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3


  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.

  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.

  3. 3.

    American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S86–104.

  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.

  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.

  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.

  7. 7.

    Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93:137–88.

  8. 8.

    American Diabetes Association. 10. Microvascular complications and foot care: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S105–18.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  25. 25.

    Investigators Gusto. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673–82.

  26. 26.

    American Diabetes Association. 6. Glycemic targets: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S55–64.

  27. 27.

    Kleinbaum DG, Klein M. Survival analysis. Berlin: Springer; 2010.

  28. 28.

    Lin D, Wei L, Ying Z. Model-checking techniques based on cumulative residuals. Biometrics. 2002;58:1–12.

  29. 29.

    Anonymous Standards of Medical Care in Diabetes-2018. Diabetes Care January 01 2018;41:s1.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  38. 38.

    National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60:850–86.

  39. 39.

    Haluzik M, Frolik J, Rychlik I. Renal effects of DPP-4 inhibitors: a focus on microalbuminuria. Int J Endocrinol. 2013;2013:895102.

  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.

  41. 41.

    Tanaka T, Higashijima Y, Wada T, Nangaku M. The potential for renoprotection with incretin-based drugs. Kidney Int. 2014;86:701–11.

Download references

Author information

Correspondence to Sukhyang Lee.

Ethics declarations

Conflicts of interest

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 59 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yoo, H., Park, I., Kim, D.J. et al. Effects of sarpogrelate on microvascular complications with type 2 diabetes. Int J Clin Pharm 41, 563–573 (2019) doi:10.1007/s11096-019-00794-7

Download citation


  • Diabetic complications
  • Nephropathy
  • Neuropathy
  • Retinopathy
  • Sarpogrelate
  • Korea