Determination of factors affecting medication adherence in type 2 diabetes mellitus patients using a nationwide claim-based database in Japan

Autoři: Takeshi Horii aff001;  Kenji Momo aff002;  Takeo Yasu aff004;  Yusuke Kabeya aff005;  Koichiro Atsuda aff001
Působiště autorů: Research and Education Center for Clinical Pharmacy, Division of Clinical Pharmacy, Laboratory of Pharmacy Practice and Science 1, Kitasato University School of Pharmacy, Kanagawa, Japan aff001;  Department of Pharmacy, The Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan aff002;  Department of Hospital Pharmaceutics, School of pharmacy, Showa University, Tokyo, Japan aff003;  Department of Medicinal Therapy Research, Pharmaceutical Education and Research Center, Meiji Pharmaceutical University, Tokyo, Japan aff004;  Department of Home Care Medicine, Sowa Hospital, Kanagawa, Japan aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



The extent of medication adherence in patients with type 2 diabetes mellitus (T2DM) several years after starting treatment with hypoglycemic agents remains unknown. Most previous work on medication adherence targeting this group of patients has been undertaken across a single year or is questionnaire based. This study aimed to determine medication adherence status and factors affecting adherence 3 years after initiation of hypoglycemic agents, using a nationwide medical claim-based database in Japan.


This retrospective study was conducted on data from 884 subjects with T2DM to better understand medication adherence, the effects of polypharmacy, and other factors. We also investigated the effects of medication nonadherence on hemoglobin A1c levels. Proportion of days covered was defined as the number of days for which a hypoglycemic agent was prescribed and in the patient’s possession to the number of days in the observation period. A proportion of days covered ≥0.8 were considered adherent, and those with a value <0.8 as nonadherence. Polypharmacy was defined as taking ≥5 medications.


Of the 884 patients investigated, 440 were considered adherent during the study period. Significant factors related to adherence included number of medications (3 or 4, or ≥5), male sex, age 50–<60 years, and total number of visits ≥17. Medication adherence was also a factor related to patients with hemoglobin A1c values < 7.0% at the end of the observation period.


We surveyed medication adherence for 3 years with post medication initiation, and found that subjects aged 50–<60 years, those with ≥3 concomitant medications, and those with a total number of visits ≥17 were more likely to be adherent and persistent, and more likely to continue their hypoglycemic agents. A high degree of medication adherence was found to have a positive influence on hemoglobin A1c levels.

Klíčová slova:

Age groups – Body Mass Index – Drug adherence – Drug therapy – Hypoglycemics


1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353: 487–497 doi: 10.1056/NEJMra050100 16079372

2. DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42: 200–209. doi: 10.1097/01.mlr.0000114908.90348.f9 15076819

3. Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J, VA Naltrexone Study Group 425. Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health. 2003;6: 566–573. doi: 10.1046/j.1524-4733.2003.65269.x 14627063

4. Waeber B, Leonetti G, Kolloch R, McInnes GT. Compliance with aspirin or placebo in the Hypertension Optimal Treatment (HOT) study. J Hypertens. 1999;17: 1041–1045. doi: 10.1097/00004872-199917070-00022 10419079

5. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23: 1296–1310. doi: 10.1016/s0149-2918(01)80109-0 11558866

6. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004;27: 1218–1224. doi: 10.2337/diacare.27.5.1218 15111553

7. Bailey CJ, Kodack M. Patient adherence to medication requirements for therapy of type 2 diabetes. Int J Clin Pract. 2011;65: 314–322. doi: 10.1111/j.1742-1241.2010.02544.x 21314869

8. Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabet Med. 2015;32: 725–737. doi: 10.1111/dme.12651 25440507

9. Fukuda H, Mizobe M. Impact of nonadherence on complication risks and healthcare costs in patients newly-diagnosed with diabetes. Diabetes Res Clin Pract. 2017;123: 55–62. doi: 10.1016/j.diabres.2016.11.007 27940390

10. Sapkota S, Brien JA, Greenfield JR, Aslani P. A systematic review of interventions addressing adherence to anti-diabetic medications in patients with type 2 diabetes–components of interventions. PLoS One. 2015; 10(2):e0118296. doi: 10.1371/journal.pone.0118296 25710465

11. Kimura S, Sato T, Ikeda S, Noda M, Nakayama T. Development of a database of health insurance claims: standardization of disease classifications and anonymous record linkage. J Epidemiol. 2010; 20: 413–419. doi: 10.2188/jea.JE20090066 20699602

12. Nakaoka S, Ishizaki T, Urushihara H, Satoh T, Ikeda S, Morikawa K, et al. Echocardiography for the detection of valvulopathy associated with the use of ergot-derived dopamine agonists in patients with Parkinson's disease. Intern Med. 2011;50: 687–694. doi: 10.2169/internalmedicine.50.4344 21467699

13. Gibson TB, Song X, Alemayehu B, Wang SS, Waddell JL, Bouchard JR, et al. Cost sharing, adherence, and health outcomes in patients with diabetes. Am J Manag Care. 2010;16: 589–600. 20712392

14. Juarez DT, Tan C, Davis J, Mau M. Factors affecting sustained medication adherence and its impact on health care utilization in patients with diabetes. J Pharm Health Serv Res. 2013;4: 89–94. doi: 10.1111/jphs.12016 23717343

15. Choudhry NK, Shrank WH, Levin RL, Lee JL, Jan SA, Brookhart MA, et al. Measuring concurrent adherence to multiple related medications. Am J Manag Care. 2009;15: 457–464. 19589013

16. Ho PM, Rumsfeld JS, Masoudi FA, McClure DL, Plomondon ME, Steiner JF, et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006;166: 1836–1841. doi: 10.1001/archinte.166.17.1836 17000939

17. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17: 230. doi: 10.1186/s12877-017-0621-2 29017448

18. Tunceli K, Zhao C, Davies MJ, Brodovicz KG, Alexander CM, Iglay K, et al. Factors associated with adherence to oral antihyperglycemic monotherapy in patients with type 2 diabetes. Patient Prefer Adherence. 2015;9: 191–197. doi: 10.2147/PPA.S71346 25670888

19. Raum E, Kramer HU, Ruter G, Rothenbacher D, Rosemann T, Szecsenyi J, et al. Medication non-adherence and poor glycaemic control in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2012;97: 377–384. doi: 10.1016/j.diabres.2012.05.026 22763108

20. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358: 2560–2572. doi: 10.1056/NEJMoa0802987 18539916

21. Jamous RM, Sweileh WM, Abu‐Taha AS, Sawalha AF, Zyoud SH, Morisky DE. Adherence and satisfaction with oral hypoglycemic medications: a pilot study in Palestine. Int J Clin Pharm. 2011;33: 942–948. doi: 10.1007/s11096-011-9561-7 21918840

22. Kreyenbuhl J, Dixon LB, McCarthy JF, Soliman S, Ignacio RV, Valenstein M. Does adherence to medications for type 2 diabetes differ between individuals with vs without schizophrenia? Schizophr Bull. 2010;36: 428–435. doi: 10.1093/schbul/sbn106 18718883

23. Ahmad NS, Ramli A, Islahudin F, Paraidathathu T. Medication adherence in patients with type 2 diabetes mellitus treated at primary health clinics in Malaysia. Patient Prefer Adherence. 2013;7: 525–530. doi: 10.2147/PPA.S44698 23814461

24. Curkendall SM, Thomas N, Bell KF, Juneau PL, Weiss AJ. Predictors of medication adherence in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2013;29: 1275–1286. doi: 10.1185/03007995.2013.821056 23815104

25. Donnan PT, MacDonald TM, Morris AD. Adherence to prescribed oral hypoglycaemic medication in a population of patients with type 2 diabetes: a retrospective cohort study. Diabet Med. 2002;19: 279–284. doi: 10.1046/j.1464-5491.2002.00689.x 11942998

26. Hertz RP, Unger AN, Lustik MB. Adherence with pharmacotherapy for type 2 diabetes: a retrospective cohort study of adults with employer sponsored health insurance. Clin Ther. 2005;27: 1064–1073. doi: 10.1016/j.clinthera.2005.07.009 16154485

27. Tiv M, Viel JF, Mauny F, Eschwege E, Weill A, Fournier C, et al. Medication adherence in type 2 diabetes: the ENTRED study 2007, a French population-based study. PLoS One. 2012;7: e32412. doi: 10.1371/journal.pone.0032412 22403654

28. Hayashino Y, Suzuki H, Yamazaki K, Izumi K, Noda M, Kobayashi M. Depressive symptoms, not completing a depression screening questionnaire, and risk of poor compliance with regular primary care visits in patients with type 2 diabetes: the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) study group. Exp Clin Endocrinol Diabetes. 2011;119: 276–280. doi: 10.1055/s-0030-1265213 21031344

29. Kurtyka K, Nishikino R, Ito C, Brodovicz K, Chen Y, Tunceli K. Adherence to dipeptidyl peptidase-4 inhibitor therapy among type 2 diabetes patients with employer-sponsored health insurance in Japan. J Diabetes Investig. 2016;7: 737–743. doi: 10.1111/jdi.12474 27182033

30. Horii T, Iwasawa M, Kabeya Y, Atsuda K. Polypharmacy and oral antidiabetic treatment for type 2 diabetes characterised by drug class and patient characteristics: A Japanese database analysis. Sci Rep. 2019 Sep 10; 9(1):12992. doi: 10.1038/s41598-019-49424-2 31506542

31. Fujihara K, Igarashi R, Matsunaga S, Matsubayashi Y, Yamada T, Yokoyama H, et al. Comparison of baseline characteristics and clinical course in Japanese patients with type 2 diabetes among whom different types of oral hypoglycemic agents were chosen by diabetes specialists as initial monotherapy (JDDM 42). Medicine. 2017;96: e6122. doi: 10.1097/MD.0000000000006122 28207538

32. Hayashino Y, Suzuki H, Yamazaki K, Goto A, Izumi K, Noda M. A cluster randomized trial on the effect of a multifaceted intervention improved the technical quality of diabetes care by primary care physicians: The Japan Diabetes Outcome Intervention Trial-2 (J-DOIT2). Diabet Med. 2016;33: 599–608. doi: 10.1111/dme.12949 26331280

33. World Health Organization. Adherence to long term therapies: Evidence for action. Geneva: World Health Organization; 2003. p. 221

34. Adams AS, Trinacty CM, Zhang F, Kleinman K, Grant RW, Meigs JB, et al. Medication adherence and racial differences in A1C control. Diabetes Care. 2008;31: 916–921. doi: 10.2337/dc07-1924 18235050

35. Trinacty CM, Adams AS, Soumerai SB, Zhang F, Meigs JB, Piette JD, et al. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study. BMC Health Serv Res. 2009;9: 24. doi: 10.1186/1472-6963-9-24 19200387

36. Nagasawa M, Smith MC, Barnes JH Jr, Fincham JE. Meta-analysis of correlates of diabetes patients' compliance with prescribed medications. Diabetes Educ. 1990;16: 192–200. doi: 10.1177/014572179001600309 2139601

37. Lawton J, Peel E, Parry O, Douglas M. Patients' perceptions and experiences of taking oral glucose-lowering agents: a longitudinal qualitative study. Diabet Med. 2008;25:491–495. doi: 10.1111/j.1464-5491.2008.02400.x 18294222

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