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Journal of Diabetes 7 (2015) 315–321
R E V I E W A RT I C L E
Adherence to insulin treatment in diabetes: can it be improved? Sheila Anne DOGGRELL1 and Vincent CHAN2 1 School of Biomedical Sciences and 2School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
Correspondence Sheila Anne Doggrell, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Gardens Point, Brisbane, GPO2434, QLD 4001, Australia. Tel: +61 7 3138 2015 Fax: +61 7 3138 1534 Email: [email protected] Received 16 March 2014; revised 20 August 2014; accepted 24 August 2014. doi: 10.1111/1753-0407.12212
Abstract Insulin is used in all subjects with Type 1 diabetes, and when Type 2 diabetes is not controlled by oral anti-diabetic medicines, insulin is also used in Type 2 diabetes. However, despite this use, there is still increased mortality and morbidity in subjects with diabetes, compared to subjects without diabetes. One of the factors, which may be involved in this increased mortality and morbidity in subjects with diabetes, is nonadherence to insulin. Nonadherence rates to insulin are in the range of 20–38%, and many factors contribute to the nonadherence. The major aim of the review was to determine whether interventions to improve adherence to insulin do actually improve adherence to insulin. Most studies have shown that adherence to insulin was improved by changing from the vial-and-syringe approach to prefilled insulin pens, but not all studies have shown that this translated into better glycemic control and clinical outcomes. The results of studies using automatic telephone messages to improve adherence to insulin to date are inconclusive. There is limited and variable evidence that an intervention by a nurse/educator, which discusses adherence to medicines, does improve adherence to insulin. In contrast, there is little or no evidence that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. In conclusion, rather than assuming that an intervention by a health professional discussing adherence to insulin actually improves adherence to insulin, long-term studies investigating this are required. Keywords: adherence, diabetes, health professional, insulin, telephone.
Introduction Diabetes is a leading cause of mortality and morbidity, and this is due to the development of optic renal, neuropathic and cardiovascular disease. Type 1 diabetes accounts for far fewer cases of diabetes mellitus than Type 2 diabetes. Insulin is the major medicine used in the treatment of Type 1 diabetes. When other medicines become inadequate in subjects with Type 2 diabetes, insulin is added. As a consequence high numbers of subjects with diabetes use insulin injections, e.g. 30% of subjects with diabetes in the US.1 Any prevention of the progression of diabetes with insulin will require good adherence to insulin.
Prior to insulin treatment, subjects with Type 1 diabetes had low life expectancy and high mortality, and when insulin was introduced as the standard treatment for Type 1 diabetes, life expectancy increased and morbidity decreased. However, despite the use of insulin, the prognosis for young subjects with Type 1 diabetes is still not ideal with a recent longitudinal study having shown retinopathy, proteinurea, and neuropathy progressed over 11 years.2 Furthermore, a recent study, between 2005 and 2007, showed that mortality in subjects with Type 1 diabetes had declined since earlier studies, but that this cohort still had a higher mortality rate than those without diabetes, and this predominantly is due to cardiovascular mortality.3
© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
315
Adherence to insulin – can it be improved?
S.A. DOGGRELL and V. CHAN
One of the factors that may be involved in this continuing increased mortality and morbidity in diabetes may be nonadherence to insulin, and adherence/ nonadherence to insulin is the subject of this review. This review also discusses whether changes/interventions to improve adherence to insulin do actually improve adherence to insulin. Finally, there is a commentary, as to whether the methods to improve adherence to insulin are adequate, and future directions.
Methods The databases searched were PubMed, CINAHL, PsychINFO and Health and Medicine Complete. For the review of the importance of adherence, rates of adherence and factors affecting adherence to insulin, the search was of “insulin” with “adherence”, “compliance”, “persistence”, “concordance” or “omission”. For the section on administration methods and improving adherence to insulin, there was an additional search of “insulin” with “administration” or “injection”. For the section on automatic telephone messages and improving the adherence to insulin, the additional search was of “insulin” with “telephone” or “SMS”. For the section on interventions by health professionals to improve adherence to insulin, the additional search was of “insulin” with “doctor”, “physician”, “pharmacist”, “nurse” or “educator”. The authors read the abstracts, which were written in English, and when it was clear that the adherence being discussed was not to insulin, but to other aspects of adherence to the management of diabetes, the abstract was not downloaded. For the other references, full papers were downloaded or collected via interlibrary loan. The authors extracted and included all papers that specifically addressed adherence to insulin and had a measure of adherence to insulin. Studies referenced in the retrieved studies on adherence to insulin that were relevant, were also collected and included.
Adherence/nonadherence to insulin and its relationship to HbA1c levels, morbidity and mortality The importance of adherence to insulin has been established both in studies measuring HbA1c levels and in trials of morbidity and mortality in subjects taking insulin for diabetes. HbA1c levels are often used as an indicator for both the management of diabetes and for the clinical outcomes. As one would predict, low adherence to insulin, measured as the medicine possession ratio (MPR), which is the number of days for which the medicine has been prescribed divided by the number of days for 316
which prescriptions have been fulfilled, is associated with higher HbA1c values, than observed with high adherence to insulin in adolescents with Type 1 diabetes4 and insulinusing adult subjects with Type 2 diabetes.5 Perhaps, rather surprisingly, a recent review that included studies of adherence to insulin and HbA1c failed to find any studies attempting to link the rate of adherence to insulin with HbA1c in adults with Type 1 diabetes.6 However, a study has shown that women with Type 1 diabetes, who restrict their insulin use, have higher HbA1c levels than nonrestrictors.7 In 234 women with Type 1 diabetes, and a mean age of 34 years, 30% self-reported insulin restriction.7 Over 11 years, there was an increased rate of death in these restrictors (10 of 71, 14%), compared to appropriate insulin users (16 of 163, 10%).7 Insulin restrictors also had higher rates of nephropathy (25% vs 10%) and foot problems (25% vs 12%).7 As HbA1c is only a surrogate marker for clinical outcomes, when considering adherence to insulin, it is important to determine the relationship between adherence to insulin and clinical outcomes, and this is discussed below. Morbidity studies have shown that nonadherence to insulin is associated with more diabetic ketoacidosis, hypoglycemia, and hospital admissions. The Diabetes Audit and Research in Tayside Scotland – Medicines Monitory Unit (DARTS/MEMO) collaboration showed that in 89 subjects with Type 1 diabetes attending a teaching hospital or young-adults diabetes clinic, there was a significant association between this nonadherence to insulin and hospital admissions for diabetic ketoacidosis, which was responsible for 15 admissions in 10 subjects in a year, and hypoglycemia (21 admissions from eight subjects) and all hospital admissions for acute complications of diabetes.4 Nonadherence to insulin is also associated with increased mortality. In 11 532 adult subjects with Type 2 diabetes, nonadherence to insulin, defined as 200 units/day, was measured as PDC (proportion of days covered).18 Only 33% and 18% of subjects taking U-500R and U-100 insulin, were ≥80% adherent, and adherence 7.5%; 24% taking insulin The Organization Program of DiabEtes Insulin ManaGement study of 1511 subjects at 48 centres throughout China, with HbA1c >7.5%
Telephone calls by a health education, trained by a certified diabetes nurse educator, compared to print information over 1 year Started on insulin therapy with trained nurses delivered education program versus normal care over 16 weeks
2010:34 No change in adherence
2009:33 40% nonadherent after 3 months 10.8%, 95 mmol/mol
Introduction of insulin treatment with education from physician and diabetes nurse educator for 3 months Reciprocal peer support versus nurse care management for 6 months
Year: ref number Adherence/nonadherence to insulin Intervention
27 low income from tertiary health care center in Mexico city
The rates of adherence to insulin, reported in this review, have been reported in three ways: self-reporting (e.g.7), visual analogue scale27 and MPR/pharmacy/medical records.4,5,8,10,23 All of these methods have limitations. Self-reporting has been shown to overestimate adherence and to underestimate nonadherence.38 The validity of prescription refill dates relies on the completeness of databases, and does not actually measure medication taking, which could be less than that for which there was
Baseline HbA1c
Underestimate of nonadherence
Participants
Commentary
Table 1
or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. There have been four studies of interventions by health professionals to improve adherence to insulin, and these are summarized in Table 1, with three studies showing no improvement in adherence to insulin.33–35 Although the OPENING (Organization Program of DiabEtes INsulIn ManaGement) study showed that adherence to insulin was improved by nurse education (Table 1), this improvement in adherence was only associated with a small benefit in glycemic control (0.16%).36 Thus, in the control group, the baseline HbA1c was 9.46% and this was reduced to 7.38% by the start of insulin with normal care, whereas in the education group, the HbA1c was reduced from 9.38% to 7.22%.36 Over the 16 weeks of the trial, the education group had their insulin dosage adjusted more often (83%) than the control group (77%), and at the end of the trial, the education group were taking a higher dose of insulin (30.4 IU) than the control group (19.1 IU).36 It is possible that this higher dose of insulin in the education than the control group may have contributed to the small benefit in glycemic control in the education group. In a 2012 pilot study of 10 adults with type 1 diabetes and depression, it was shown that an intervention that offered two visits with a certified diabetes nurse educator, three visits with a registered dietitian, and 10–12 sessions of cognitive-behavioral therapy for adherence and depression improved adherence in the seven subjects who completed.37 Adherence was self-reported of how often they took their insulin, and increased from 77% before to 87% after the intervention.37 In addition, there was a decrease in depression severity, insulin monitoring, and a modest decrease in HbA1c from 9.6% (81 mmol/ mol) to 9.0% (75 mmol/mol).37 There are several problems with this study including the lack of a control group, low numbers of subjects, and high self-reported adherence.
Adherence to insulin – can it be improved?
Effect of intervention by health professionals on adherence to insulin in subjects with type 2 diabetes
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prescription refills.38 Thus, it is possible that the rates of nonadherence to insulin given in this review are underestimated, and the problem is more serious than has been reported. Better methods of measuring adherence, including adherence to insulin, are needed to get a definitive answer to this. Automatic telephone messaging To date the evidence with automatic telephone messaging to improve adherence to insulin is not conclusive. Sweet Talk showed a small improvement in adherence to insulin without improvement in HbA1c,28 and a separate small short-term study suggested improvements in injections of insulin in the evening.29 Thus, there is a need for a larger, longer trial of automatic telephone messaging to determine its effects on insulin adherence. Conclusions relating to interventions by health professionals One of the most interesting findings of this review was that there is no conclusive evidence that an intervention by a health professional that discusses adherence to insulin actually improves adherence to insulin. There is some evidence that an intervention by a nurse/educator that discusses adherence to insulin may improve this adherence, but this is not found in all studies. However, there is little or no evidence (to our knowledge) that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. Rather than assuming that this is the case, long-term studies investigating whether adherence to insulin can be improved by interventions by health professionals are required.
Acknowledgement There was no funding of this article.
Disclosure The authors have no conflicts of interest.
References 1. Percentage of adults with diagnosed diabetes receiving treatment with insulin or oral medication, United States, 2007–2009. Available from: http://www.cdc.gov/diabetes/ pubs/pdf/factsheet11_figures.pdf (accessed 23 October 2014). 320
2. Bryden KS, Dunger DB, Mayou RA, Peveler RC, Neil HA. Poor prognosis of young adults with type 1 diabetes: A longitudinal study. Diabetes Care. 2003; 26: 1052–7. 3. Livingstone SJ, Looker HC, Hothersall EJ et al. Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish Registry Linkage Study. PLoS Med. 2012; 9: e1001321. 4. Morris AD, Boyle DI, McMahon AD et al. Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/ MEMO collaboration. Diabetes audit and research in Tayside Scotland. Medicines Monitoring Unit. Lancet. 1997; 350: 1505–10. 5. Donnelly LA, Morris AD, Evans JM, DARTS/MEMO collaboration. Adherence to insulin and its association with glycaemic control in patients with type 2 diabetes. QJM. 2007; 100: 345–50. 6. Asche C, Lafleur J, Conner C. A review of diabetes treatment adherence and the association with clinical and economic outcomes. Clin Ther. 2011; 33: 74–109. 7. Goebel-Fabbri AE, Fikkan J, Franko DL et al. Insulin restriction and associated morbidity and mortality in women with type 1 diabetes. Diabetes Care. 2008; 31: 415–19. 8. Ho PM, Rumsfeld JS, Masoudi FA et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006; 166: 1836–41. 9. Weisserg-Benchell J, Glasgow AM, Tynan WG, Wirtz P, Turek J, Ward J. Adolescent diabetes management and mismanagement. Diabetes Care. 1995; 18: 77–82. 10. Burdick J, Chase HP, Slover RH et al. Missed insulin meal boluses and elevated haemoglobin A1c levels in children receiving insulin pump therapy. Pediatrics. 2004; 113: e221–4. 11. Pan´Kowska E, Skórka A, Szypowska A, Lipka M. Memory of insulin pumps and their record as a source of information about insulin therapy in children and adolescents with type 1 diabetes. Diabetes Technol Ther. 2005; 7: 308–14. 12. Olinder AL, Kernell A, Smide B. Missed bolus doses: Devastating for metabolic control in CSII-treated adolescents with type 1 diabetes. Pediatr Diabetes. 2009; 10: 142–8. 13. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004; 27: 1218– 24. 14. Brown JB, Nichols GS, Glauber HS, Bakst A. Ten-year follow-up of antidiabetic drug use, nonadherence, and mortality in a defined population with type 2 diabetes mellitus. Clin Ther. 1999; 21: 1045–57. 15. Rajagopalan R, Joyce A, Smith D, Ollendorf D, Murray FT. Medication compliance in type 2 diabetes patients: Retrospective data analysis (Abstact). Value Health. 2003; 6: 328. 16. Cramer JA, Pugh MJ. The influence of insulin use on glycemic control: How well do adults follow prescriptions for insulin? Diabetes Care. 2005; 26: 78–83. 17. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insulin adherence behaviours and barriers in the
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18.
19.
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23.
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27.
multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabet Med. 2012; 29: 682–9. Eby EL, Wang P, Curtis BH et al. Cost, healthcare utilization, and adherence of individuals with diabetes using U-500 or U-100 insulin: A retrospective database analysis. J Med Econ. 2013; 16: 529–38. Polonsky WH, Anderson BJ, Lohrer RA et al. Insulin omission in women with IDDM. Diabetes Care. 1994; 17: 1178–85. Peyrot M, Rubin RR, Kruger DF, Luther LB. Correlates of insulin injection omission. Diabetes Care. 2010; 33: 240–5. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insulin adherence bahaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy Study. Diabet Med. 2012; 29: 682–9. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Factors associated with injection omission/nonadherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab. 2012; 14: 1081–7. Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Medication adherence and the associated health-economic impact among patients with type 2 diabetes mellitus converting to insulin pen therapy: An analysis of third-party managed care claims data. Clin Ther. 2006; 28: 1712– 25. Cobden D, Lee WC, Balu S, Joshi AV, Pashos CL. Health outcomes and economic impact of therapy conversion to a biphasic insulin analog pen among privately insured patients with type 2 diabetes mellitus. Pharmacotherapy. 2007; 27: 948–62. Baser O, Bouchard J, DeLuzio T, Henk H, Aagren M. Assessment of adherence and healthcare costs of insulin device (FlexPen™) versus conventional vial/syringe. Adv Ther. 2010; 27: 94–104. Lee LJ, Li Q, Reynolds MW, Pawaskar MD, Corrigan SM. Comparison of utilization, cost, adherence, and hypoglcemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/ syringe. J Med Econ. 2011; 14: 75–86. Xie L, Zhou S, Wei W, Gill J, Pan C, Baser O. Does pen help? A real-world outcomes study of switching from vial
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to disposable pen among insulin glargine-treated patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2013; 15: 230–6. Franklin VL, Waller A, Pagliari C, Green SA. A randomized trial of Sweet Talk, a text-messaging system to support young people with diabetes. Diabetic Med. 2006; 23: 1332–8. Louch G, Dalkin S, Bodansky J, Conner M. An exploratory randomised controlled trial using short messaging service to facilitate insulin administration in young adults with type 1 diabetes. Psychol Health Med. 2013; 18: 166– 74. Davidson MB. The effectiveness of nurse- and pharmacist-directed care in diabetes disease management: A narrative review. Current Diabetes Reviews. 2007; 3: 280–6. Vivian EM. The pharmacist’s role in maintaining adherence to insulin therapy in type 2 diabetes mellitus. Consult Pharm. 2007; 22: 320–32. Grossman S. Management of type 2 diabetes mellitus in the elderly: Role of the pharmacist in multidisciplinary health care team. J Multidiscip Healthc. 2011; 4: 149–54. Lerman I, Díaz JPM, Ibarguengoitia MER et al. Nonadherence to insulin therapy in low-income, type 2 diabetic patients. Endocr Prac. 2009; 15: 41–6. Heisler M, Vijan S, Makki F, Piette JD. Diabetes control with reciprocal support versus nurse care management – A randomized trial. Ann Intern Med. 2010; 153: 507–15. Walker EA, Blanco E, Shmukler C et al. Results of a successful telephonic intervention to improve diabetic control in urban adults – A randomised trial. Diabetes Care. 2011; 34: 2–7. Guo XH, Ji LN, Lu JM et al. Efficacy of structured education in patients with type 2 diabetes mellitus receiving insulin treatment. J Diabetes. 2014; 6: 290–7. Markowitz SM, Carper MM, Gonzalez JS, Delahanty LM, Safren SA. Cognitive-behavioral therapy for the treatment of depression and adherence in patients with type 1 diabetes: Pilot data and feasibility. Prim Care Companion CNS Disorder. 2012; 14: doi:10.4088/ PCC.11m01220. Hearnshaw H, Lindenmeyer A. What do we mean by adherence to treatment and advice for living with diabetes? A review of the literature on definitions and measurements. Diabet Med. 2006; 23: 720–8.
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Journal of Diabetes 7 (2015) 315–321
R E V I E W A RT I C L E
Adherence to insulin treatment in diabetes: can it be improved? Sheila Anne DOGGRELL1 and Vincent CHAN2 1 School of Biomedical Sciences and 2School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
Correspondence Sheila Anne Doggrell, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Gardens Point, Brisbane, GPO2434, QLD 4001, Australia. Tel: +61 7 3138 2015 Fax: +61 7 3138 1534 Email: [email protected] Received 16 March 2014; revised 20 August 2014; accepted 24 August 2014. doi: 10.1111/1753-0407.12212
Abstract Insulin is used in all subjects with Type 1 diabetes, and when Type 2 diabetes is not controlled by oral anti-diabetic medicines, insulin is also used in Type 2 diabetes. However, despite this use, there is still increased mortality and morbidity in subjects with diabetes, compared to subjects without diabetes. One of the factors, which may be involved in this increased mortality and morbidity in subjects with diabetes, is nonadherence to insulin. Nonadherence rates to insulin are in the range of 20–38%, and many factors contribute to the nonadherence. The major aim of the review was to determine whether interventions to improve adherence to insulin do actually improve adherence to insulin. Most studies have shown that adherence to insulin was improved by changing from the vial-and-syringe approach to prefilled insulin pens, but not all studies have shown that this translated into better glycemic control and clinical outcomes. The results of studies using automatic telephone messages to improve adherence to insulin to date are inconclusive. There is limited and variable evidence that an intervention by a nurse/educator, which discusses adherence to medicines, does improve adherence to insulin. In contrast, there is little or no evidence that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. In conclusion, rather than assuming that an intervention by a health professional discussing adherence to insulin actually improves adherence to insulin, long-term studies investigating this are required. Keywords: adherence, diabetes, health professional, insulin, telephone.
Introduction Diabetes is a leading cause of mortality and morbidity, and this is due to the development of optic renal, neuropathic and cardiovascular disease. Type 1 diabetes accounts for far fewer cases of diabetes mellitus than Type 2 diabetes. Insulin is the major medicine used in the treatment of Type 1 diabetes. When other medicines become inadequate in subjects with Type 2 diabetes, insulin is added. As a consequence high numbers of subjects with diabetes use insulin injections, e.g. 30% of subjects with diabetes in the US.1 Any prevention of the progression of diabetes with insulin will require good adherence to insulin.
Prior to insulin treatment, subjects with Type 1 diabetes had low life expectancy and high mortality, and when insulin was introduced as the standard treatment for Type 1 diabetes, life expectancy increased and morbidity decreased. However, despite the use of insulin, the prognosis for young subjects with Type 1 diabetes is still not ideal with a recent longitudinal study having shown retinopathy, proteinurea, and neuropathy progressed over 11 years.2 Furthermore, a recent study, between 2005 and 2007, showed that mortality in subjects with Type 1 diabetes had declined since earlier studies, but that this cohort still had a higher mortality rate than those without diabetes, and this predominantly is due to cardiovascular mortality.3
© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
315
Adherence to insulin – can it be improved?
S.A. DOGGRELL and V. CHAN
One of the factors that may be involved in this continuing increased mortality and morbidity in diabetes may be nonadherence to insulin, and adherence/ nonadherence to insulin is the subject of this review. This review also discusses whether changes/interventions to improve adherence to insulin do actually improve adherence to insulin. Finally, there is a commentary, as to whether the methods to improve adherence to insulin are adequate, and future directions.
Methods The databases searched were PubMed, CINAHL, PsychINFO and Health and Medicine Complete. For the review of the importance of adherence, rates of adherence and factors affecting adherence to insulin, the search was of “insulin” with “adherence”, “compliance”, “persistence”, “concordance” or “omission”. For the section on administration methods and improving adherence to insulin, there was an additional search of “insulin” with “administration” or “injection”. For the section on automatic telephone messages and improving the adherence to insulin, the additional search was of “insulin” with “telephone” or “SMS”. For the section on interventions by health professionals to improve adherence to insulin, the additional search was of “insulin” with “doctor”, “physician”, “pharmacist”, “nurse” or “educator”. The authors read the abstracts, which were written in English, and when it was clear that the adherence being discussed was not to insulin, but to other aspects of adherence to the management of diabetes, the abstract was not downloaded. For the other references, full papers were downloaded or collected via interlibrary loan. The authors extracted and included all papers that specifically addressed adherence to insulin and had a measure of adherence to insulin. Studies referenced in the retrieved studies on adherence to insulin that were relevant, were also collected and included.
Adherence/nonadherence to insulin and its relationship to HbA1c levels, morbidity and mortality The importance of adherence to insulin has been established both in studies measuring HbA1c levels and in trials of morbidity and mortality in subjects taking insulin for diabetes. HbA1c levels are often used as an indicator for both the management of diabetes and for the clinical outcomes. As one would predict, low adherence to insulin, measured as the medicine possession ratio (MPR), which is the number of days for which the medicine has been prescribed divided by the number of days for 316
which prescriptions have been fulfilled, is associated with higher HbA1c values, than observed with high adherence to insulin in adolescents with Type 1 diabetes4 and insulinusing adult subjects with Type 2 diabetes.5 Perhaps, rather surprisingly, a recent review that included studies of adherence to insulin and HbA1c failed to find any studies attempting to link the rate of adherence to insulin with HbA1c in adults with Type 1 diabetes.6 However, a study has shown that women with Type 1 diabetes, who restrict their insulin use, have higher HbA1c levels than nonrestrictors.7 In 234 women with Type 1 diabetes, and a mean age of 34 years, 30% self-reported insulin restriction.7 Over 11 years, there was an increased rate of death in these restrictors (10 of 71, 14%), compared to appropriate insulin users (16 of 163, 10%).7 Insulin restrictors also had higher rates of nephropathy (25% vs 10%) and foot problems (25% vs 12%).7 As HbA1c is only a surrogate marker for clinical outcomes, when considering adherence to insulin, it is important to determine the relationship between adherence to insulin and clinical outcomes, and this is discussed below. Morbidity studies have shown that nonadherence to insulin is associated with more diabetic ketoacidosis, hypoglycemia, and hospital admissions. The Diabetes Audit and Research in Tayside Scotland – Medicines Monitory Unit (DARTS/MEMO) collaboration showed that in 89 subjects with Type 1 diabetes attending a teaching hospital or young-adults diabetes clinic, there was a significant association between this nonadherence to insulin and hospital admissions for diabetic ketoacidosis, which was responsible for 15 admissions in 10 subjects in a year, and hypoglycemia (21 admissions from eight subjects) and all hospital admissions for acute complications of diabetes.4 Nonadherence to insulin is also associated with increased mortality. In 11 532 adult subjects with Type 2 diabetes, nonadherence to insulin, defined as 200 units/day, was measured as PDC (proportion of days covered).18 Only 33% and 18% of subjects taking U-500R and U-100 insulin, were ≥80% adherent, and adherence 7.5%; 24% taking insulin The Organization Program of DiabEtes Insulin ManaGement study of 1511 subjects at 48 centres throughout China, with HbA1c >7.5%
Telephone calls by a health education, trained by a certified diabetes nurse educator, compared to print information over 1 year Started on insulin therapy with trained nurses delivered education program versus normal care over 16 weeks
2010:34 No change in adherence
2009:33 40% nonadherent after 3 months 10.8%, 95 mmol/mol
Introduction of insulin treatment with education from physician and diabetes nurse educator for 3 months Reciprocal peer support versus nurse care management for 6 months
Year: ref number Adherence/nonadherence to insulin Intervention
27 low income from tertiary health care center in Mexico city
The rates of adherence to insulin, reported in this review, have been reported in three ways: self-reporting (e.g.7), visual analogue scale27 and MPR/pharmacy/medical records.4,5,8,10,23 All of these methods have limitations. Self-reporting has been shown to overestimate adherence and to underestimate nonadherence.38 The validity of prescription refill dates relies on the completeness of databases, and does not actually measure medication taking, which could be less than that for which there was
Baseline HbA1c
Underestimate of nonadherence
Participants
Commentary
Table 1
or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. There have been four studies of interventions by health professionals to improve adherence to insulin, and these are summarized in Table 1, with three studies showing no improvement in adherence to insulin.33–35 Although the OPENING (Organization Program of DiabEtes INsulIn ManaGement) study showed that adherence to insulin was improved by nurse education (Table 1), this improvement in adherence was only associated with a small benefit in glycemic control (0.16%).36 Thus, in the control group, the baseline HbA1c was 9.46% and this was reduced to 7.38% by the start of insulin with normal care, whereas in the education group, the HbA1c was reduced from 9.38% to 7.22%.36 Over the 16 weeks of the trial, the education group had their insulin dosage adjusted more often (83%) than the control group (77%), and at the end of the trial, the education group were taking a higher dose of insulin (30.4 IU) than the control group (19.1 IU).36 It is possible that this higher dose of insulin in the education than the control group may have contributed to the small benefit in glycemic control in the education group. In a 2012 pilot study of 10 adults with type 1 diabetes and depression, it was shown that an intervention that offered two visits with a certified diabetes nurse educator, three visits with a registered dietitian, and 10–12 sessions of cognitive-behavioral therapy for adherence and depression improved adherence in the seven subjects who completed.37 Adherence was self-reported of how often they took their insulin, and increased from 77% before to 87% after the intervention.37 In addition, there was a decrease in depression severity, insulin monitoring, and a modest decrease in HbA1c from 9.6% (81 mmol/ mol) to 9.0% (75 mmol/mol).37 There are several problems with this study including the lack of a control group, low numbers of subjects, and high self-reported adherence.
Adherence to insulin – can it be improved?
Effect of intervention by health professionals on adherence to insulin in subjects with type 2 diabetes
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Adherence to insulin – can it be improved?
S.A. DOGGRELL and V. CHAN
prescription refills.38 Thus, it is possible that the rates of nonadherence to insulin given in this review are underestimated, and the problem is more serious than has been reported. Better methods of measuring adherence, including adherence to insulin, are needed to get a definitive answer to this. Automatic telephone messaging To date the evidence with automatic telephone messaging to improve adherence to insulin is not conclusive. Sweet Talk showed a small improvement in adherence to insulin without improvement in HbA1c,28 and a separate small short-term study suggested improvements in injections of insulin in the evening.29 Thus, there is a need for a larger, longer trial of automatic telephone messaging to determine its effects on insulin adherence. Conclusions relating to interventions by health professionals One of the most interesting findings of this review was that there is no conclusive evidence that an intervention by a health professional that discusses adherence to insulin actually improves adherence to insulin. There is some evidence that an intervention by a nurse/educator that discusses adherence to insulin may improve this adherence, but this is not found in all studies. However, there is little or no evidence (to our knowledge) that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. Rather than assuming that this is the case, long-term studies investigating whether adherence to insulin can be improved by interventions by health professionals are required.
Acknowledgement There was no funding of this article.
Disclosure The authors have no conflicts of interest.
References 1. Percentage of adults with diagnosed diabetes receiving treatment with insulin or oral medication, United States, 2007–2009. Available from: http://www.cdc.gov/diabetes/ pubs/pdf/factsheet11_figures.pdf (accessed 23 October 2014). 320
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