Clinical and Experimental Nephrology

, Volume 21, Issue 4, pp 694–704 | Cite as

Impact of the use of anti-diabetic drugs on survival of diabetic dialysis patients: a 5-year retrospective cohort study in Taiwan

  • Po-Jen Hsiao
  • Kun-Lin Wu
  • Szu-Han Chiu
  • Jenq-Shyong Chan
  • Yuh-Feng Lin
  • Chung-Ze Wu
  • Chia-Chao Wu
  • SenYeong Kao
  • Te-Chao Fang
  • Shih-Hua Lin
  • Jin-Shuen ChenEmail author
Original article



Type 2 diabetes mellitus (DM) and associated complications are common in patients with chronic kidney disease (CKD) and can increase morbidity and mortality. A longitudinal 5-year observational study was conducted to investigate whether the use of anti-diabetic medications or not affected survival rates of diabetic dialysis patients.


Using a data sample of a million patients from Taiwan’s National Health Insurance Database, a retrospective cohort study surveyed patients with type 2 DM who began dialysis between 2002 and 2007. The study population was classified into groups using or not using anti-diabetic drugs. The group using anti-diabetic drugs was then categorized into 3 subgroups, including use of only oral hypoglycemic agents (OHAs), only insulin, and OHAs-combined insulin groups. Subjects of these four groups were followed 5 years or to date of death. Three major areas were analyzed: (1) demographic data and medical history; (2) survival prognosis and causes of death; and (3) effects on survival prognosis of different classes of OHAs.


A total of 912 patients fitting inclusion criteria were enrolled and followed-up for 5 years or to date of death. A total 465 patients died, and those not using anti-diabetic drugs (67.34 %) had a higher mortality rate than those using anti-diabetic drugs (46.42 %). After the multivariate analysis, group of OHAs-combined insulin had the lowest risk of death (HR 0.36, 95 % CI 0.27–0.47), followed by OHAs alone (HR 0.49, 95 % CI 0.38–0.63) and then insulin alone (HR 0.67, 95 % CI 0.51–0.88). To clarify four classes of OHAs (sulfonylurea, α-glucosidase inhibitors, meglitinide, and thiazolidinedione) are used in Taiwan for uremia patient with type 2 DM, and in our study, there were no significant differences in survival prognosis for the four drugs. Finally, the most common cause of death was infectious disease and there were no significant differences among the four groups.


This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OHAs should play an important role in treating these patients.


Anti-diabetic drugs Oral hypoglycemic agents Insulin Dialysis Diabetes mellitus Survival 



This work is supported by grants from the National Science Council (MOST 104-2314-B-016-036), and the Tri-Service General Hospital (TSGH-C104-007-S02), Taiwan, ROC. We deeply appreciate Professor Mary Goodwin’s (English department, National Taiwan Normal University) efforts in the language support. This study could not have been carried out without the cooperation and support of the Bureau of National Health Insurance (NHI), National Health Research Institutes, the Dialysis Registry System of the Taiwan Society of Nephrology, and the Institutional Review Board of the Tri-Service General Hospital (TSGH), National Defense Medical Center. We deeply appreciate Professor Mary Goodwin’s (English department, National Taiwan Normal University) efforts in the language support.

Compliance with ethical standards

Conflict of interest

All the authors declare that there is no conflict of interest in this study.

Informed consents

All data in this study was from Taiwan’s National Health Insurance Research Database (NHIRD); we could not obtain informed consents from individual participants.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee, at which the studies were conducted (IRB approval number TSGH-C102-17) and with the 1964 Helsinki declaration and comparable ethical standards.


  1. 1.
    Snyder RW, Berns JS. Use of insulin and oral hypoglycemic medications in patients with diabetes mellitus and advanced kidney disease. Semin Dial. 2004;17:365–70.CrossRefPubMedGoogle Scholar
  2. 2.
    Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl. 2011;2015(5):2–7.Google Scholar
  3. 3.
    Kiefer MM, Ryan MJ. Primary care of the patient with chronic kidney disease. Med Clin North Am. 2015;99:935–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.CrossRefPubMedGoogle Scholar
  5. 5.
    Action to Control Cardiovascular Risk in Diabetes Study G, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger J, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358:2545–59.Google Scholar
  6. 6.
    Hsu PF, Sung SH, Cheng HM, Yeh JS, Liu WL, Chan WL, et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care. 2013;36:894–900.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Morioka T, Emoto M, Tabata T, Shoji T, Tahara H, Kishimoto H, et al. Glycemic control is a predictor of survival for diabetic patients on hemodialysis. Diabetes Care. 2001;24:909–13.CrossRefPubMedGoogle Scholar
  8. 8.
    Oomichi T, Emoto M, Tabata T, Morioka T, Tsujimoto Y, Tahara H, et al. Impact of glycemic control on survival of diabetic patients on chronic regular hemodialysis: a 7-year observational study. Diabetes Care. 2006;29:1496–500.CrossRefPubMedGoogle Scholar
  9. 9.
    McMurray SD, Johnson G, Davis S, Mc-Dougall K. Diabetes education and care management significantly improve patient outcomes in the dialysis unit. Am J Kidney Dis. 2002;40:566–75.CrossRefPubMedGoogle Scholar
  10. 10.
    Lee MJ, Kwon YE, Park KS, Kee YK, Yoon CY, Han IM, et al. Glycemic control modifies difference in mortality risk between hemodialysis and peritoneal dialysis in incident dialysis patients with diabetes: results from a nationwide prospective cohort in Korea. Medicine (Baltimore). 2016;95:e3118.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63:713–35.CrossRefPubMedGoogle Scholar
  12. 12.
    Rosenstock J, Marx N, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, et al. Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CARO-LINA trial. Diab Vasc Dis Res. 2013;10:289–301.CrossRefPubMedGoogle Scholar
  13. 13.
    Holman RR, Bethel MA, Chan JC, Chiasson JL, Doran Z, Ge J, et al. Rationale for and design of the acarbose cardiovascular evaluation (ACE) trial. Am Heart J. 2014;168:23–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Schramm TK, Gislason GH, Vaag A, Rasmussen JN, Folke F, Hansen ML, et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J. 2011;32:1900–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J. 2015;36:2288–96.CrossRefPubMedGoogle Scholar
  16. 16.
    Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F. The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci. 2013;9:936–43.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2007;292:E871–83.CrossRefPubMedGoogle Scholar
  18. 18.
    DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, et al. Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates. Diabetes. 2013;62:3920–6.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Finegood DT, McArthur MD, Kojwang D, Thomas MJ, Topp BG, Leonard T, et al. Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes. 2001;50:1021–9.CrossRefPubMedGoogle Scholar
  20. 20.
    DeFronzo RA, Tripathy D, Abdul-Ghani M, Musi N, Gastaldelli A. The disposition index does not reflect beta-cell function in IGT subjects treated with pioglitazone. J Clin Endocrinol Metab. 2014;99:3774–81.CrossRefPubMedGoogle Scholar
  21. 21.
    Nicholls SJ, Tuzcu EM, Wolski K, Bayturan O, Lavoie A, Uno K, et al. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (pioglitazone effect on regression of intravascular sonographic coronary obstruction prospective evaluation) study. J Am Coll Cardiol. 2011;57:153–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Davidson M, Meyer PM, Haffner S, Feinstein S, D’Agostino R Sr, Kondos GT, et al. Increased high-density lipoprotein cholesterol pre-dicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation. 2008;117:2123–30.CrossRefPubMedGoogle Scholar
  23. 23.
    Sarafidis PA, Nilsson PM. The effects of thiazolidinediones on blood pressure levels—a systematic review. Blood Press. 2006;15:135–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Derosa G, Fogari E, Cicero AF, D’Angelo A, Ciccarelli L, Piccinni MN, et al. Blood pressure control and inflamma-tory markers in type 2 diabetic patients treated with pioglitazone or rosiglitazoneand metformin. Hypertension Res. 2007;30:387–94.CrossRefGoogle Scholar
  25. 25.
    Natali A, Baldeweg S, Toschi E, Capaldo B, Barbaro D, Gastaldelli A, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care. 2004;27:1349–57.CrossRefPubMedGoogle Scholar
  26. 26.
    Martens FM, Visseren FL, de Koning EJ, Rabelink TJ. Short-term pioglitazone treatment improves vascular function irrespective of metabolic changes in patients with type 2 diabetes. J Cardiovasc Pharmacol. 2005;46:773–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Hanefeld M, Pfutzner A, Forst T, Kleine I, Fuchs W. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study. Cardiovasc Diabetol. 2011;10:65.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Schernthaner G. Pleiotropic effects of thiazolidinediones on traditional and non-traditional atherosclerotic risk factors. Int J Clin Pract. 2009;63:912–29.CrossRefPubMedGoogle Scholar
  29. 29.
    Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–89.CrossRefPubMedGoogle Scholar
  30. 30.
    Erdmann E, Charbonnel B, Wilcox RG, Skene AM, Massi-Benedetti M, Yates J, et al. Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes Care. 2007;30:2773–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Erdmann E, Harding S, Lam H, Perez A. Ten-year observational follow-up of PROactive: a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes. Diabetes Obes Metab. 2016;18:266–73.CrossRefPubMedGoogle Scholar
  32. 32.
    Tobey TA, Greenfield M, Kraemer F, Reaven GM. Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. Metabolism. 1981;30:165–71.CrossRefPubMedGoogle Scholar
  33. 33.
    Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire JL, Keenan JF, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361:1736–47.CrossRefPubMedGoogle Scholar
  34. 34.
    Gamble JM, Simpson SH, Eurich DT, Majumdar SR, Johnson JA. Insulin use and increased risk of mortality in type 2 diabetes: a cohort study. Diabetes Obes Metab. 2010;12:47–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Currie CJ, Poole CD, Evans M, Peters JR, Morgan CL. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapiesin type 2 diabetes. J Clin Endocrinol Metab. 2013;98:668–77.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL, et al. Survivial as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375:481–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Colayco DC, Niu F, McCombs JS, Cheetham TC. A1C and cardiovascular outcomes in type 2 diabetes: a nested case-control study. Diabetes Care. 2011;34:77–83.CrossRefPubMedGoogle Scholar
  38. 38.
    Yajima T, Yajima K, Hayashi M, Yasuda K, Takahashi H, Yamakita N. Serum albumin-adjusted glycated albumin is a better predictor of mortality in diabetic patients with end-stage renal disease on hemodialysis. J Diabetes Complicat. 2016.Google Scholar
  39. 39.
    Brunelli SM, Thadhani R, Ikizler TA, Feldman HI. Thiazolidinedione use is associated with better survival in hemodialysis patients with non-insulin dependent diabetes. Kidney Int. 2009;75:961–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Querci F, et al. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients. Metabolism. 2010;59:887–95.CrossRefPubMedGoogle Scholar
  41. 41.
    Matsubara J, Sugiyama S, Akiyama E, Iwashita S, Kurokawa H, Ohba K, et al. Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J. 2013;77:1337–44.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2016

Authors and Affiliations

  • Po-Jen Hsiao
    • 1
    • 2
  • Kun-Lin Wu
    • 1
    • 2
  • Szu-Han Chiu
    • 3
  • Jenq-Shyong Chan
    • 1
    • 2
  • Yuh-Feng Lin
    • 1
    • 4
    • 5
  • Chung-Ze Wu
    • 6
  • Chia-Chao Wu
    • 1
  • SenYeong Kao
    • 7
  • Te-Chao Fang
    • 8
  • Shih-Hua Lin
    • 1
  • Jin-Shuen Chen
    • 1
    Email author
  1. 1.Division of Nephrology, Department of Internal Medicine, Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan
  2. 2.Division of Nephrology, Department of Internal MedicineTaoyuan Armed Forces General HospitalTaoyuanTaiwan
  3. 3.Division of Metabolism, and Endocrinology, Department of Internal MedicineTaoyuan Armed Forces General HospitalTaoyuanTaiwan
  4. 4.Division of Nephrology, Department of MedicineShuang Ho HospitalTaipeiTaiwan
  5. 5.Graduate Institute of Clinical MedicineTaipei Medical UniversityTaipeiTaiwan
  6. 6.Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho HospitalTaipei Medical UniversityNew Taipei CityTaiwan
  7. 7.School of Public HealthNational Defense Medical CenterTaipeiTaiwan
  8. 8.Division of Nephrology, Department of Internal Medicine, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan

Personalised recommendations