The challenge of patient adherence in managing type 2 diabetes

by S. A. Ross, Canada

Stuart A. ROSS, FRPC Endocrinologist, LMC Calgary Clinical Professor of Medicine University of Calgary CANADA

The prevalence of type 2 diabetes continues to increase. To reduce vascular complications, patients are frequently requested to follow a complex medical regimen including diet, exercise and multiple drug therapies. Despite the proven benefits of reaching therapeutic targets, studies have shown that less than 50% of patients will reach their glycemic goals. In part, this may be due to nonadherence in following a prescribed therapeutic regimen. The World Health Organization has defined adherence as the extent to which a person’s behavior—taking medication, following diet, and/or executing lifestyle changes—corresponds with agreed recommendations from a health care provider. Nonadherence can lead to a failure to reach glycemic targets, resulting in vascular complications with an associated increase in morbidity, mortality, and health costs. Multiple factors influence medication nonadherence, and they can be individually addressed. These modifiable factors include complexity of treatment regimens, side effect profile of prescribed drugs, multiple drug therapies, failure of communication by the health care provider, psychosocial issues, and cost. Communication becomes a key in improving adherence. Information from the health care professional should be reviewed by the patient to ensure that the patient understands the proposed therapy and will follow directions. Each patient will have an individual approach to a specific concern and will offer solutions that are suitable and attractive to them. Their views must be listened to and reviewed, and an agreed course of action should be determined. Simplification of complex therapies can greatly improve adherence. The use of fixed-dose combination drugs will reduce the pill burden, and using medication blister packs and convenient medication reminders can provide improved adherence and the achievement of glycemic targets.

There is no question that the worldwide increase in the prevalence of type 2 diabetes has led to major population health care concerns. It is estimated that 11% of the US adult population have diabetes, and the number of patients affected continues to increase on a yearly basis.1 Diabetes remains a major cause of mortality. In terms of morbidity, the associated vascular complications of diabetes have led to a significant increase in the expenditure of health care dollars. In the United States, health care costs for diabetes have reached an annual cost of $245 billion.2

Recent years have seen the development of increasingly sophisticated treatment methods to manage type 2 diabetes. Clinical trials have consistently demonstrated that lowering the A1c values leads to a major decrease in microvascular complications. While diet and exercise regimens remain a cornerstone of management, the development of new classes of glucose-lowering medications has provided more opportunities to achieve specific glucose targets. In addition, recent cardiac outcome trials have further demonstrated that specific drugs can provide considerable benefit in reducing serious cardiac events.3-5

Despite these advances, it is recognized that less than 50% of patients with diabetes will actually achieve their stated glycemic target. In a 2013 Canadian study of over 5000 patients, only 50% reached their prescribed A1c target of <7% despite well-established national programs for diabetes management.6 In addition, utilization of available glucose-lowering drugs was low among the participants despite their failure to reach glycemic targets. Of those failing to reach target, 18% were on a single noninsulin anti-hyperglycemic agent (NIAHA) (which was metformin in 85% of cases), 15% were on two NIAHAs, 6% were on three NIAHAs, and only 19% were on insulin.

These data suggest that either physicians are not advocating and implementing appropriate treatments, or patients are refusing or are not compliant with a specific treatment regimen. Potential difficulties in achieving stated glycemic goals are listed in Table I.

Table I. Potential difficulties in achieving stated glycemic goals.


A variety of terms have been used to describe the ability of a patient to follow a specific medical regimen, including adherence, compliance, and persistence. The World Health Organization (WHO) has recommended the use of the term “adherence” and has defined adherence to therapy as “the extent to which a person’s behavior—taking medication, following a diet, and/or executing lifestyle changes—corresponds with agreed recommendations from a health care provider.”7 The WHO identified medication nonadherence as a leading cause of health care costs and preventable morbidity and mortality.7

The impact of nonadherence

Reaching target A1c levels has been proven to decrease the risk of microvascular disease. Yet nonadherence to medication in patients with diabetes has been shown to be a major cause of failure to reach glycemic targets and leads to a significant increase in A1c values, with a 10% increase in nonadherence leading to at least a 0.1% increase in A1c values. In addition, for every 10% decrease in adherence there is a significant increase in emergency room visits and hospitalizations. Jha et al determined that improved adherence to diabetes medications was associated with 13% lower odds of subsequent hospitalizations or emergency department visits. At the same time, a loss of adherence was associated with 15% higher odds of these outcomes. In the United States, the cost of poor adherence is estimated at $8.3 billion every year.8-12

In type 2 patients with diabetes being treated with antihypertensive, antihyperglycemic, and statin drugs, nonadherence leads to a significant increase in both mortality and hospitalizations.13 A further study indicated that although improved adherence increases pharmacy costs, it also leads to substantial medical savings as a result of fewer hospitalizations and emergency department visits.14

Assessing adherence

Various techniques have been utilized to assess and measure adherence and all provide insight into the complexities of medication nonadherence and allow for the development of new initiatives to improve adherence to prescribed therapy. Measurements of adherence include both direct and indirect methodologies such as ongoing measurements of A1c and glucose, which will assess both the efficacy of specific therapies and adherence to medications. Measurement of pill utilization and retrospective analyses of medical and pharmacy databases can provide ongoing assessment of adherence.15-17 Electronic review of whether prescriptions have been refilled at the pharmacy can also provide specific data on how effectively and regularly patients utilize regular prescriptions.18 The medication possession ratio is a more precise method that measures days of medication collected as a proportion of days of medication prescribed over a particular period, thereby enabling accurate assessment of adherence.

Table II. Morisky scale. Interpretation: A score of 6 or less strongly correlates
with poor adherence.
After reference 19: Morisky et al. J Clin Hypertens (Greenwich). 2008;10:348-354.

Clinical tools can also be used for a quick assessment of whether a patient is adherent to the medication regimen. The Morisky scale (Table II), originally designed to assess adherence to antihypertensive agents, is an easy-to-use clinical tool to help identify patients with poor medication adherence.19 In addition, the scale can help predict whether glycemic control will subsequently worsen, leading to increased morbidity and mortality.20

The development of electronic medical records has provided another tool to quickly identify functionally refractory patients where nonadherence may play a role. Aronson et al demonstrated that by using a registry to identify hyperglycemic patients, specific treatments could be utilized, resulting in significantly improved glycemic control in otherwise refractory patients with persistently elevated HbA1c.21

Factors affecting adherence to medication

Multiple factors influence medication nonadherence and in many situations these can be individually addressed, providing improved adherence and thus greater success in managing the person with diabetes. These modifiable factors include: complexity of treatment regimens; side effect profile of prescribed drugs; multiple drug therapies, failure of communication by the health care provider, psychosocial issues, and cost.

The WHO provided an extensive review of the concerns related to medication adherence.7 In their discussion they identified adherence as a multidimensional phenomenon determined by the interplay of five sets of factors. They further commented that the common belief that patients are solely responsible for taking their treatment is misleading and most often reflects a misunderstanding of how other factors affect people’s behavior and capacity to adhere to their treatment. The five categories of factors identified by the WHO include those related to the health system, the patient’s condition, the patient, the therapy, and socioeconomic considerations (Table III, page 180).

Low socioeconomic status may put patients in the position of having to choose between competing priorities such as those of other family members. The cost of medications also provides a major barrier to adherence. Patients with a lower socioeconomic status or those required to pay for their therapies will have much lower adherence to the prescribed regimen. Increasing a patient’s share of the cost of the medication has also been shown to lead to a significant decrease in adherence.17,22

Strategies to enhance adherence7

♦ Assessment of adherence
A simple discussion between the health care professional and the patient and their family will often uncover medication nonadherence. Demonstrating empathy during the discussion can frequently clarify the difficulties the patient is experiencing with taking the medication. If patients are not actually following a prescribed regimen, then it becomes important to understand the reasons for nonadherence. Simple questionnaires such as the Morisky medication adherence scale can quickly alert the physician that there is need for concern. Feedback from the dispensing pharmacy may provide an alert that the patient is not refilling prescriptions or taking medications.

♦ Empowerment and communication
When the clinician provides education and recommends a specific and possibly complex regimen, the patient receiving the care must then attempt to follow through on all the recommendations. This requires the health care provider to become the expert, while the person with diabetes must adopt an uninformed help-seeker role. This one-sided discussion does not always provide the best outcome as the opinion and thoughts of the patient are not reflected in the proposed therapeutic regimen. Communication becomes a key to achieving the therapeutic targets of both the health care professional and the patient. With improved communication, the patient is more likely to achieve self-management goals and to adopt attitudes that will lead to greater adherence and well-being.23

When changes in therapy are being suggested, it is important to explain to the patient why these changes might be required and the various therapeutic advantages and disadvantages. Adherence interventions should be tailored to the needs of the patient in order to achieve maximum impact. If there are issues such as drug side effects or increased costs, the risks and benefits of these new therapies need to be obvious to the patients and their families. With this approach, there is a greater “buy-in” to the recommendations. Unfortunately, while many health care professionals believe they are achieving these communication goals, patients and their families often see the interaction in a very different light. The DAWN1 and DAWN2 studies (Diabetes Attitudes Wishes and Needs) have exposed considerable differences between how health care professionals, patients, and their families remember a medical discussion. While the health care professionals believe that they have succeeded in communicating the issues clearly, the patients may report that they did not receive the information in a helpful manner and do not believe that they were active participants in the decision-making for their own treatment. If these divisions can be bridged, then the opportunity of improved adherence becomes more of a reality.24,25

Table III. Factors affecting adherence to medication.

It is essential to recognize that communication in a medical conference between health care provider and patient must be “two-way.” Communication becomes a key in improving adherence. Information from the health care professional should be reviewed by the patient to allow understanding and subsequent directions, by the patient, of the proposed therapy. Each patient will have an individual approach to a specific concern and will offer solutions that are suitable and attractive to them. Their views must be listened to and reviewed, and an agreed course of action should be determined.

The advent of electronic technologies has provided other tools to assist with adherence. Many patients do not have easy access to their health care professional, nor the benefit of ongoing advice as to their ongoing diabetes management. Failure to reach the proposed glycemic targets may instill a sense of failure in the patient who may decrease or even stop the prescribed medications.

Glucose meters now provide technologies such as Bluetooth that can automatically send data into a computer and onward to the health care professional for review, allowing rapid feedback. Similarly, telephone calls between patient and health care provider can allow reassurance and new directions for the person with diabetes. More recently, Internet protocols that allow easy uploading of glucose data from a glucose meter to a secure website has permitted rapid interactions between patient and health care provider. All these tools enhance the communication between patient and health care provider, thus improving adherence.26,27

♦ Education
Education is another key factor in establishing the goal of increased adherence. If a new drug is to be initiated, it is important to explain the expected benefits but at the same time outline any expected side effects and negative aspects of the new therapy. There is a need to provide full instructions on dosage and administration of the new therapy, and in particular to provide ways to reduce potential side effects or negative experiences. If the patient fully understands the new therapy, its risks and benefits, and becomes a “partner” in the new regimen, then the chances of its success are much higher.

Often, the health care professional will have choices as to which medication to initiate to achieve new targets. At that time, there needs to be careful consideration of all aspects of a new drug therapy, including efficacy, side effect profile, costs, and ease of administration. This will vary with each individual patient. Some may have concerns about the side effect profile of the therapy, while others may find cost a major issue. Each patient will often have a solution to the concern and may suggest a proposed course of action.

The concept of a composite end point, which includes multiple individual outcomes that should be met simultaneously, has become an accepted direction in choosing appropriate drug therapies. In managing the person with diabetes, a common composite end point has been the combination of three simultaneous goals: the achievement of the proposed A1c target (often <7%), no weight gain, and no hypoglycemic episodes. With the advent of newer antihyperglycemic drugs, this composite becomes an achievable goal allowing increased adherence.28

♦ Simplification of therapy
As a medication regimen becomes more complex, there will be decreased adherence. The mere process of simplifying the medication regimen frequently leads to improved adherence. Elderly patients may have multiple comorbidities requiring other treatments, thus increasing the pill burden. Other factors such as dependency on caregivers, dementia, or limited income can all contribute to decreased adherence to a prescribed regimen.

The advent of fixed-dose combination therapies has provided the greatest benefit in simplifying complex medical therapies. As a drug therapy is intensified or becomes more complex, there is a marked decrease in adherence. In a study of 91 patients with diabetes receiving oral antihyperglycemic agents, an assessment was made of compliance when drug therapies were intensified. When the drug was administered once daily, 79.1% were compliant with the prescribed regimen. But when the drug was prescribed twice a day, compliance fell to 65.6%, and when prescribed three times a day, it was reduced to 38.1%.29

The advantage of using a fixed combination therapy rather than dual therapy was demonstrated in a study reviewing patients being transferred from monotherapy to dual therapies. When patients with type 2 diabetes were switched from monotherapy to a fixed combination dual therapy, the medication possession ratio fell by 1.5% but when patients were placed on the same therapies given as two separate agents, it fell by 10 %, indicating a marked advantage to fixed combination therapies.30-32 Table IV summarizes the strategies that can be used to simplify therapy.

Table IV. Strategies to simplify therapy.


Diabetes is a complex, progressive disease requiring therapeutic interventions such as diet, exercise, and drug therapies. Despite the proven benefits of diabetes therapies, adherence to prescribed treatments is often low, leading to vascular complications with an increase in morbidity, mortality, and health costs. The reasons for nonadherence are multifactorial. These modifiable factors include failure of communication between the health care provider and the patient and their family, complexity of treatment regimens, fear of drug side effects, multiple drug therapies, psychosocial issues, and cost.

Improving adherence involves a comprehensive approach with the patient. The possibility of nonadherence must be carefully reviewed with the patient, their families, and key health care providers such as the pharmacist. Once identified, nonadherence can be addressed and thoughtful therapeutic approaches put in place. Communication becomes a key in allowing full discussion between health care professional and patient. The reasons for the proposed therapeutic regimen need to be fully discussed and the patient’s input sought and followed.

The use of fixed-dose drug combinations can greatly improve adherence. By reducing the pill burden and providing convenient times to take medications, patients are more likely to follow a prescribed drug regimen.

The development of electronic and Internet tools has permitted much greater interaction between patient and health care professional on a regular basis. Information and therapy concerns can be quickly conveyed by the patient to the health care professional, who in turn, can provide benefit to the patient.

Adherence to a prescribed therapeutic regimen is of benefit to the patient and to the health care system and is a goal that is readily achievable with today’s technologies.■

Keywords: adherence; communication; fixed-dose combination therapy; type 2 diabetes

1. International Diabetes Federation. IDF Diabetes Atlas. 5th ed. Brussels, Belgium: International Diabetes Federation; 2011.
2. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36:1033-1046.
3. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117-2128.
4. Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER trial investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
5. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375:1834-1844.
6. Leiter LA, Berard L, Bowering CK, et al. Type 2 diabetes mellitus management in Canada: is it improving? Can J Diabetes. 2013;37:82-89.
7. World Health Organization. Adherence to long-term therapies: evidence for action. Geneva, Switzerland: World Health Organization; 2003.
8. Jha AK, Aubert RE, Yao J, Teagarden JR, Epstein RS. Greater adherence to diabetes drugs is linked to less hospital use and could save nearly $5 billion annually. Health Aff (Millwood). 2012;31:1836-1846.
9. Rozenfeld Y, Hunt JS, Plauschinat C, Wong KS. Oral antidiabetic medication adherence and glycemic control in managed care. Am J Manag Care 2008;14: 71-75.
10. Schectman JM, Nadkarni MM, Voss JD. The association between diabetes metabolic control and drug adherence in an indigent population. Diabetes Care. 2002;25:1015-1021.
11. Zhu VJ, Tu W, Marrero DG, Rosenman MB, Overhage JM. Race and medication adherence and glycemic control: findings from an operational health information exchange. AMIA Annu Symp Proc. 2011;2011:1649-1657.
12. Pladevall M, Williams LK, Potts LA, Divine G, Xi H, Lafata JE. Clinical outcomes and adherence to medications measured by claims data in patients with diabetes. Diabetes Care. 2004;27:2800-2805.
13. Ho PM, Rumsfeld JS, Masoudi FA, et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Int Med. 2006;166:1836-1841.
14. Roebuck MC, Liberman JN, Gemmill-Toyama M, Brennan TA. Medication adherence leads to lower health care use and costs despite increased drug spending. Health Aff (Millwood). 2011;30:91-99.
15. Currie CJ, Peyrot M, Morgan CL, et al. The impact of treatment noncompliance on mortality in people with type 2 diabetes. Diabetes Care. 2012;35:1279- 1284.
16. Dailey G, Kim MS, Lian JF. Patient compliance and persistence with anti-hyperglycemic therapy: evaluation of a population of type 2 diabetic patients. J Int Med Res. 2002;30:71-79.
17. Tunceli K, Zhao C, Davies MJ, et al. Factors associated with adherence to oral antihyperglycemic monotherapy in patients with type 2 diabetes. Patient Prefer Adherence. 2015;9:191-197.
18. Tamblyn R, Eguale T, Huang A, Winslade N, Doran P. The incidence and determinants of primary nonadherence with prescribed medication in primary care: a cohort study. Ann Int Med. 2014;160:441-450.
19. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich). 2008;10:348-354.
20. Aikens JE, Piette JD. Longitudinal association between medication adherence and glycaemic control in Type 2 diabetes. Diabet Med. 2013;30:338-344.
21. Aronson R, Orzech N, Ye C, Brown RE, Goldenberg R, Brown V. Specialist-Led Diabetes Registries and Prevalence of Poor Glycemic Control in Type 2 Diabetes: The Diabetes Registry Outcomes Project for A1C Reduction (DROP A1C). Diabetes Care. 2016;39:1711-1717.
22. Eaddy MT, Cook CL, O’Day K, Burch SP, Cantrell CR. How patient cost-sharing trends affect adherence and outcomes: a literature review. P T. 2012;37: 45-55.
23. Jones A, Vallis M, Cooke D, Pouwer F. Working Together to Promote Diabetes Control: A Practical Guide for Diabetes Health Care Providers in Establishing a Working Alliance to Achieve Self-Management Support. J Diabetes Res. 2016;2016:2830910.
24. Peyrot M, Burns KK, Davies M, et al. Diabetes Attitudes Wishes and Needs 2 (DAWN2): A multinational, multi-stakeholder study of psychosocial issues in diabetes and person-centred diabetes care. Diabetes Res Clin Pract. 2013; 99:174-184.
25. Vallis M, Burns KK, Hollahan D, Ross S, Hahn J. Diabetes Attitudes, Wishes and Needs Second Study (DAWN2): Understanding Diabetes-Related Psychosocial Outcomes for Canadians with Diabetes. Can J Diabetes. 2016;40:234-241.
26. Tildesley HD, Po MD, Ross SA. Internet Blood Glucose Monitoring Systems Provide Lasting Glycemic Benefit in Type 1 and 2 Diabetes A Systematic Review. Med Clin N Am. 2015;99:17-33.
27. Iyengar V, Wolf A, Brown A, Close K. Challenges in Diabetes Care: Can Digital Health Help Address Them? Clinical Diabetes. 2016;34:133-141.
28. Ross SA. A multiplicity of targets: evaluating composite endpoint studies of the GLP-1 receptor agonists in type 2 diabetes. Curr Med Res Opin. 2015;31:125- 135.
29. Paes AH, Bakker A, Soe-Agnie CG. Impact of dosage frequency on patient compliance. Diabetes Care. 1997;20:1512-1517.
30. Cheong C, Barner JC, Lawson KA, Johnsrud MT. Patient adherence and reimbursement amount for antidiabetic fixed-dose combination products compared with dual therapy among Texas Medicaid recipients. Clin Ther. 2008;30: 1893-1907.
31. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86:304-314.
32. World Health Organization. Annex I: Behavioural mechanisms explaining adherence. In: Adherence to long-term therapies – Evidence for action. Geneva, Switzerland: World Health Organization; 2003.