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Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus
The American Journal of Medicine (2005) Vol 118 (5A), 27S–34S
Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus Richard R. Rubin, PhD Departments of Medicine and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. KEYWORDS: Adherence; Pharmacologic therapy; Type 2 diabetes mellitus
Many patients who have type 2 diabetes mellitus (DM) require several different medications. Although these agents can substantially reduce diabetes-related morbidity and mortality, the extent of treatment benefits may be limited by a lack of treatment adherence. Unfortunately, little information is available on treatment adherence in patients with type 2 DM. Available data indicate substantial opportunity for improving clinical outcomes through improved treatment adherence. Factors that appear to influence adherence include the patient’s comprehension of the treatment regimen and its benefits, adverse effects, medication costs, and regimen complexity, as well as the patient’s emotional well-being. Outcomes research emphasizes the importance of effective patient–provider communication in overcoming some of the barriers to adherence. This article offers specific suggestions for improving adherence in patients with type 2 DM seen in general clinical practice. © 2005 Elsevier Inc. All rights reserved.
Many patients who have type 2 diabetes mellitus (DM) require several different medications. In a US survey of adults treated with glucose-lowering medication, 50% reported using ⱖ7 medications in their prescribed treatment regimen, including ⱖ2 glucose-lowering agents.1 The reason for the large numbers of prescriptions is clear: evidence shows that tight control of blood glucose, cholesterol, and blood pressure helps these patients stay healthy. In fact, the potential for better outcomes has never been greater for those who adhere to their regimens. The number of pharmacologic agents prescribed and the number of patients who need them are growing at a disturbingly fast pace due to the type 2 DM epidemic. Improved treatment adherence may close the gap between potential treatment benefits and the benefits patients actually receive.1-4 However, despite the importance of adherence for patients
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0002-9343/$ -see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2005.04.012
with type 2 DM, surprisingly little is known about the problems related to medication adherence in this disease state.5 This article discusses what is known about estimated adherence rates, factors affecting adherence, and interventions to facilitate adherence in the type 2 DM patient population.
Adherence rates In 1995, Mason and colleagues6 and Matsuyama and coworkers7 studied 47 patients with type 2 DM. They assessed treatment adherence using medication containers with electronic monitoring systems that counted the number of times a patient opened them. Assessment of medication adherence by provider, patient self-report, and pill counts was less reliable for explaining metabolic control than was the electronic monitoring system. Since that time, ⬃20 studies of treatment adherence in patients with type 2 DM have been reported, with most published in the past few years (Table 1).8-25 These studies are inclusive of several that used protocols requiring electronic monitoring8-10 and retrospective studies that used
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The American Journal of Medicine, Vol 118 (5A), May 2005 Table 1
Treatment adherence in patients with type 2 diabetes mellitus
Type of medication
No. of Studies
Adherence Rate (%)
Oral blood glucose–lowering Insulin Blood pressure, cholesterol-lowering
25 2 3
65–85* 60–80 75–90
*The adherence rate was lower (36%–54%) for certain agents, regimens, and populations.
Table 2
Factors influencing treatment adherence
Factor
Critical Issues
Comprehension of regimen
● ● ● ● ● ● ● ● ● ● ●
Perception of benefits
Side effects Medication costs Regimen complexity Emotional well-being
Health literacy Clinician’s use of jargon Closing the communication loop Medications provide limited symptom relief Personally meaningful long-term benefit critical Role of clinician’s attitudes toward medication Vary by agent Rarely discussed Rarely discussed Adherence to timing may be greatly affected Benefits of treating depression, diabetes distress
large prescription databases maintained by pharmacy benefits managers, health maintenance organizations, Medicaid, or national health services.11-14 Most of these studies reported that adherence to oral blood glucose–lowering therapy ranged from 65% to 85%,2,6-12,14-19 although a few reported lower rates (36%–54%) for certain patient populations (eg, Medicaid recipients)13 and regimens (those requiring more frequent dosing).16,20,21 Due to the small number of studies, differences in study designs, and variations in the findings, little is known specifically about adherence to oral blood glucose–lowering medications in patients with type 2 DM. Even less is known about adherence to insulin, blood pressure–lowering, and lipid-lowering therapies in these patients. The few studies that are available suggest that self-reported adherence to blood pressure–lowering and lipid-lowering medication regimens may be a bit higher than adherence to oral glucose– lowering regimens,22-24 whereas adherence to insulin regimens may be slightly lower.17,25 Whether adherence rates are high or low, there is substantial room for improvement.
Factors influencing adherence Comprehension of the treatment regimen Of the factors that may affect treatment adherence (Table 2), perhaps the most common and most overlooked is
patients’ comprehension of the treatment regimen, which clinicians often overestimate. Schillinger and coworkers26 studied 408 English-speaking and Spanish-speaking patients in public hospitals and found that ⬎50% of both groups had limited health literacy, defined as comprehension of common medical terms or concepts (eg, stable blood pressure) and/or instructions, such as for dosing (eg, take this medication 4 times a day). Lack of patient comprehension often goes unrecognized by physicians, who rarely verify patients’ recall and comprehension of their treatment regimens. In another study by Schillinger’s group,27 office visits of patients with type 2 DM were audiotaped to determine how often physicians introduced a new concept (e.g., a treatment-adjustment recommendation) and how often they assessed patients’ recall and comprehension of that concept. In 82% of office visits, ⱖ1 new concept was introduced, at least half of which concerned a treatment adjustment. Physicians assessed patient recall and comprehension in only 12% of these situations. The mean duration of visits in which recall and comprehension were assessed was similar to that of visits in which they were not. Furthermore, patients whose physicians assessed recall and comprehension had lower glycosylated hemoglobin (Hb) A1c concentrations than those patients whose physicians did not assess recall. This study demonstrates the need for and impact of effective physician–patient communication regarding treatment regimens.
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For patients with type 2 DM, health literacy also includes understanding instructions for self-care (including treatment adherence)28 and glycemic control, as well as concepts such as patient outcomes and medication costs.28,29 Ensuring effective communication means clarifying and restating messages until a patient’s recall and comprehension are verified. A study conducted in 2001 by Ciechanowski and colleagues30 found that patients who rated the communication provided by their physicians as good were significantly more adherent to oral blood glucose–lowering regimens (P ⬍0.05) and to recommendations for self-monitoring blood glucose (P ⬍0.01) than those patients who rated their physicians as poor communicators. Others found similar advantages in treatment satisfaction,27,31 glycemic control,32 and health status33 among patients reporting good communication with their healthcare providers.
Perception of treatment benefits Effective provider–patient communication can help clinicians address other factors that influence treatment adherence, including patients’ perceptions of the potential benefits of adherence. A study by Grant and associates22 emphasized that patients are more likely to adhere to treatments they perceive as helpful in alleviating their symptoms than to those they do not. Because hypertension and dyslipidemia in some patients with type 2 DM are not associated with any recognizable signs or symptoms, care must be taken by physicians to communicate effectively to patients who may not be aware of the potential benefits of treating an asymptomatic condition. Additionally, many patients do not recognize the symptoms of hyperglycemia. Clinicians can help patients understand the short-term benefits of glycemic control (e.g., increased energy, better quality sleep, fewer school days or workdays missed) and remind patients that using medication as prescribed contributes to attaining these benefits. Patients’ perceptions of treatment benefits are also influenced by clinicians’ attitudes and practices regarding antidiabetic medications. In a multinational survey of patients with type 2 DM and their physicians,34 59% and 43% of physicians indicated that they preferred to delay insulin and oral antihyperglycemia therapies, respectively, until they were essential. In addition, when asked how often they told patients they will have to start insulin if they do not follow medical advice, 57% of physicians responded either “always” or “often.” Given these physicians’ attitudes and practices, it may not be surprising that many patients surveyed had negative attitudes and, consequently, were not using insulin.35 For example, only 23% of these patients reported believing that insulin therapy would help them manage their DM, and 48% reported believing that being prescribed insulin therapy was an indication that they had failed to follow their treatment regimen correctly. The influence of physicians’ attitudes and behaviors on patient treatment adherence requires further investigation. In the meantime, physi-
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cians should recognize the impact their own attitudes and behaviors may have on patients and take the time to communicate effectively with their patients about the long-term benefits of prescribed medications.
Regimen complexity Many patients with type 2 DM are prescribed complex treatment regimens to help them achieve glycemic goals. Several retrospective database studies have shown that rates of adherence to polytherapy regimens were 10% to 20% lower than those for monotherapy regimens.13,16,21 Paes and colleagues8 used electronic monitoring to compare adherence to medications dosed once, twice, or thrice daily. To determine whether agents were taken at the prescribed times, the monitoring system tracked not only how often the medication containers were opened but also precisely when. The adherence rate for once-daily dosing was 79%; those for 2 and 3 times daily dosing decreased to 66% and 38%, respectively. Furthermore, medications were taken at the prescribed times in 77% of cases of once-daily dosing; the rate fell to 41% and 5%, respectively, for dosing 2 and 3 times daily. These findings suggest that prescribing medications that require fewer doses can increase medication adherence. However, physicians should bear in mind another finding of this study: ⬎33% of patients used more medication than prescribed, and these were primarily patients whose medications were dosed once a day. Patients must fully comprehend the prescribed regimen, and must have a dependable system for monitoring medicine that has been taken.
Perceived adverse effects Adverse effects (AEs) (i.e., hypoglycemia, weight gain) as well as agent tolerability, drug– drug interactions and complicated drug regimens lead some patients to use medications prescribed for the treatment of type 2 DM, hypertension, and high cholesterol levels either less often than prescribed or not at all. In a study by Boccuzzi and colleagues,11 after 12 months of metformin therapy 60% of patients were still adherent to their medication regimen, whereas 12-month persistence rates for sulfonylureas, repaglinide, and ␣-glucosidase inhibitors were lower (56%, 48%, and 31%, respectively). In a study of 128 patients using ⱖ3 medications concurrently, 21% were not perfectly adherent to their regimens.22 Of these, ⬎70% were perfectly adherent to all but 1 agent. AEs were the most common reason for lack of adherence, were fairly serious, and were long lasting (⬎30 days). However, AEs were rarely addressed in office visits: ⬍25% of patients mentioned them to their healthcare providers. Clearly, patients should be asked about AEs, and their treatment should be adjusted accordingly.
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Medication costs
that they received treatment for these problems. Another report estimated that only 25% of patients with type 2 DM who experienced depression received adequate treatment for it.42 Identifying and treating depression and DM-related emotional distress can contribute to improved treatment adherence and other positive outcomes. Physicians can identify patients at risk for distress or depression by regularly discussing symptoms with the patient or by using a validated screening questionnaire, such as the Patient Health Questionnaire–9,43 the Beck Depression Inventory,44 or the Center for Epidemiological Studies Depression Scale.45 Furthermore, effective treatment of distress or depression has been associated with improved metabolic outcomes. Several small, short-term (8- to 10-week), randomized clinical trials have shown that treatments for depression effective in the general population were also effective in patients with type 2 DM. In separate studies, the active treatments nortriptyline,46 fluoxetine,47 and cognitive-behavioral therapy (CBT) plus DM education48 were compared with controls (placebo and DM education alone, respectively); in each study, the severity of depressive symptoms was significantly reduced with the active treatment compared with controls (P ⫽ 0.03, P ⬍0.01, P ⬍0.001, respectively). Nortriptyline was not statistically more effective than placebo in reducing HbA1c levels in depressed patients (P ⫽ 0.5), but there was a trend toward greater reduction in HbA1c in patients treated with fluoxetine, compared with those taking placebo (P ⫽ 0.13), and HbA1c levels were significantly lower at follow-up in patients receiving CBT plus education than in patients receiving education alone (P ⫽ 0.03). Effective treatment of distress and depression could lead to improved glycemic control directly49 or by increasing motivation and changing behavior, including increasing treatment adherence.
Medication costs can affect adherence. In a US survey of adults with type 2 DM receiving blood glucose–lowering therapy, 11% indicated that they had limited their medications in the past year due to cost, with 7% having cut back in the past month.1 Predictably, patients with little or no prescription-drug coverage had more difficulty affording medications than those whose prescriptions were mostly or completely covered. Provider–patient communication concerning cost seems limited. Of respondents who indicated medication cutbacks, only 32% reported informing their providers of the cutback, and 37% said they had not discussed medication costs with their providers. Furthermore, clinicians do not seem to be doing everything possible to prevent cost as a barrier to adherence. About 70% of patients indicated that their providers had not raised the issue of medication costs, and only ⬃10% reported being given information on sources of lowcost medications or financial assistance programs. A similar proportion of patients (⬃10%) reported that their providers had prescribed fewer medications to decrease out-of-pocket expenses. The reasons patients provided for not discussing cost with their clinicians point toward opportunities for improvement: 50% did not believe their healthcare provider could help with costs, 39% did not believe cost was important enough to mention, 35% felt embarrassed, and 30% felt there was not enough time during their visits to talk about it. Clinicians should ask their patients about cost-related problems with treatment adherence and make it clear that cost is an important issue, and should not cause embarrassment, given the high cost of medications and other necessities. Clinicians should also offer information on sources of inexpensive medications and financial assistance programs and make treatment adjustments as appropriate to minimize costs.
Emotional well-being In a study by Peyrot and associates,36 investigators found that almost 70% of clinicians responding to the Diabetes Attitudes Wishes and Needs (DAWN) survey reported that psychological problems (including stress and depression) affected treatment adherence in their patients with type 2 DM. Clinicians seem to recognize that depression and DMrelated emotional distress (eg, frustration with symptoms, disease management) can decrease concentration, energy, self-sufficiency, motivation, and self-care while increasing blood glucose levels, healthcare costs, and the risk for diabetic complications.12,36-41 Unfortunately, although clinicians recognize the impact of psychological problems on medical outcomes, patients with type 2 DM rarely receive psychological treatment. In the DAWN survey, almost 50%of patients reported specific psychological problems and poor psychological well-being, but only 10% indicated
Methods to improve adherence Verifying recall and comprehension Several methods have been used to improve treatment adherence (Table 3), including verifying recall and comprehension. Physicians can verify patients’ recall and comprehension of treatment regimens by asking patients to restate dosing instructions and recommended treatment changes. Physicians should ask questions not to “test” the patient, but in a way that indicates that they are simply checking to ensure they have communicated clearly (e.g., “Just to be sure I’ve been clear, tell me your understanding of when you should take the medication.”). Using pictures of medication facilitates recall and comprehension in some patients (e.g., “Just to be clear, let’s review the instructions for all your medications. Here are pictures of the pills you should take; tell me when you should take this one.”).
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Adherence to Pharmacologic Therapy in Patients with Type 2 Diabetes Mellitus Table 3
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Interventions to facilitate treatment adherence
Goal/target
Intervention
Enhance regimen recall/ comprehension
● Verify patient’s understanding while in the office ● Use visual aids ● Clarify limited symptom relief ● Find meaningful long-term benefits ● Discuss and monitor ● Make adjustments ● Discuss and monitor ● Change regimen when appropriate ● Monitor ● Change regimen when appropriate ● Screen for depression ● Treat depressed patients or refer ● Screen for diabetes-related distress ● Facilitate problem solving ● Refer for diabetes education
Enhance perceived benefits of regimen
Minimize adverse effects Minimize costs
Minimize regimen complexity Facilitate emotional well-being
Clarifying potential treatment benefits Patients should be helped to understand that they will not feel the benefits of some medications that are prescribed to protect future health. The clinician could say, “Can you feel the benefits of your blood pressure and cholesterol pills? If you are like most people, the answer is no. But those pills help keep your blood pressure and cholesterol level where they belong; reduce your risk for a heart attack or stroke; and help you live a longer, healthier life. You take these pills because you want to stay healthy in the future. What is your biggest reason for wanting to stay healthy in the future?” Some people feel the short-term benefits of glucoselowering medication and should be encouraged to identify these benefits. A clinician could say, “When they take their medication as prescribed, some people notice their blood sugar control improves. Have you noticed that? If so, does better control change anything in your life? Some people say they have more energy, sleep better, are sick less often, or miss fewer days of work. Are any of those things true for you?”
Simplifying regimens Clinicians can ask questions to identify any adherence problems related to regimen complexity: “Of all your medications, which are you most likely to skip or forget, and when? How often do you skip or forget them? Why do you skip them?” Clinicians can offer a simpler treatment regi-
men (fewer medications or less frequent dosing) or suggest systems to help the patient remember to take medications on time and keep track of what was taken.
Electronic monitoring In a study by Matsuyama and colleagues,7 physicians and pharmacists used data from electronic monitoring to help them make appropriate medication adjustments. These data were most helpful in determining whether hyperglycemia was related to an inadequate prescription or to missed doses. In a randomized controlled trial by Rosen and associates,10 17 patients in the intervention group engaged in a structured dialogue with a healthcare provider about daily medication dosing using the patients’ own electronic monitoring devices. This intervention led to improved adherence in this group compared with controls (n ⫽ 16), who received no intervention, although the change in HbA1c concentration was statistically similar between the 2 groups. Another trial by Piette and colleagues50 evaluated the effect of telephone calls from a physician’s office on adherence and outcomes. Twenty-eight patients in an intervention group received biweekly automated calls that assessed health status and provided self-care education. A nurse made follow-up calls to patients who reported problems. The intervention group averaged 1.4 completed automated calls per month, and the mean duration of contact with a nurse was 6 minutes per month. After 12 months, compared with a group receiving usual care, the intervention group reported better treatment adherence (all P ⱕ0.03), fewer
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DM symptoms (P ⬍0.0001), and lower (0.3%) HbA1c concentrations. Although electronic monitoring and automated telephone assessment and support systems generally are not available, elements of these successful strategies that will improve patient outcomes can be incorporated into general clinical practice.
for and treat depression or refer these patients for treatment. The following 9 symptoms are characteristic of depression: (1) depressed mood, (2) anhedonia (loss of interest and pleasure), (3) change in sleep, (4) change in appetite or weight, (5) low energy, (6) psychomotor agitation or retardation, (7) poor concentration, (8) low self-esteem or guilt, and (9) recurrent thoughts of death. At least 1 of the 2 cardinal symptoms— depressed mood and anhedonia— must be present for a diagnosis of major depression as defined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.52 A patient could have depression but not mention depressed mood; anhedonia might be the primary symptom. Clinicians can screen for depression by asking questions about depressed mood and anhedonia— e.g., “During the past 2 weeks, have you felt down, depressed, or hopeless? Have you lost interest or pleasure in doing things you once enjoyed?” If the answer to one or both questions is affirmative, the clinician then should ask about the remaining 7 symptoms of depression. A variety of validated self-report questionnaires for depression screening also are available.43-45 Most patients can complete any of the widely used depression screeners in ⬍5 minutes, and the results can be obtained in ⬍2 minutes, so the results should be available to discuss at the same visit. CBT and antidepressants are effective treatments for depression in patients with DM. Although most patients experience a full response to antidepressant medication within 6 weeks,42 some require 12 weeks, so patients should be prepared for the possibility of delayed benefits to avoid disappointment and premature discontinuation of the medication. Patients should be carefully monitored for remission of depressive symptoms and for AEs. Insomnia, agitation, and loss of libido are common in patients receiving treatment with a selective serotonin reuptake inhibitor or related medications, especially fluoxetine and paroxetine. Techniques for managing AEs include starting at a low dose, adding an agent to manage the AE, or switching agents. Referral to a mental healthcare professional is appropriate if the diagnosis is in doubt, if the patient has a complicated psychiatric history, or if the patient does not respond to antidepressant medication or experiences ⱖ1 serious AE. Patients who do not have depression may still experience diabetes-related emotional distress. Clinicians should identify these patients and formulate treatment interventions to address the sources of distress. The Problem Areas in Diabetes survey, developed by Polonsky and colleagues,41 can help clinicians assess a patient’s overall level of DM-related emotional distress as well as its specific sources (e.g., sources that may represent barriers to treatment adherence).
Minimizing costs To help minimize cost-related adherence problems, clinicians should know the approximate out-of-pocket costs of various agents, as well as sources of low-cost medications and financial-assistance programs. They should ask directly about cost-related adherence problems, just as they do about AEs: “The medication I just prescribed will cost you about $50 a month in co-payments. Will that be a problem for you?” If the answer is yes, the physician can explore further. Difficulty affording medications should be monitored consistently. For example, a clinician might say, “Medication costs are a real problem for many people. Are you having trouble paying for any of your medications? If you are, what are you doing about it? Have you cut back on any of your medications? If so, which ones, and by how much? Have you cut back on other things to pay for your medicine?” Clinicians should also offer to change the regimen if appropriate, and provide information on sources of low-cost medications or financial assistance.
Discussing adverse effects Clinicians can minimize barriers to medication adherence by titrating doses and discussing potential AEs with their patients. The nature and course of common AEs should be described. Patients should also be strongly encouraged to call the clinician if interactions or AEs arise. Making a correction 1 or 2 weeks after the original adjustment is preferable to making it at the patient’s next visit several months later. This method also reinforces the provider– patient relationship and helps ensure that patients will return for follow-up visits. Follow-up visits are the most effective way to improve treatment adherence; many patients who are not seen regularly are unlikely to adhere to their treatment regimens.51 Medications should be monitored at each visit with some simple questions: “How are things going with your medication? Are you having any problems?” If a patient does not mention any, he or she should be asked about specific AEs that commonly occur with that agent. In fact, clinicians should regularly ask about AEs for all medications.
Minimizing depression or diabetes-related emotional distress Depression and diabetes-related emotional distress require treatment because of their substantial impact on treatment adherence and patient outcomes. Clinicians can screen
Summary Education is a useful resource for addressing all barriers to treatment adherence in patients with type 2 DM. Studies
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Adherence to Pharmacologic Therapy in Patients with Type 2 Diabetes Mellitus
show that self-management education improves patients’ understanding, confidence, and level of self-care, and leads to improvement in self-care behavior, glycemic control, and good patient outcomes.53-55 Working with patients to enhance treatment adherence helps to strengthen and maintain a collaborative patient– provider relationship. Patients who are satisfied with their provider–patient relationship are more likely to return for follow-up, which is the most powerful predictor of treatment adherence and other self-care behaviors.
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17. Rajagopalan R, Joyce A, Smith D, Ollendorf D, Murray FT. Medication compliance in type 2 diabetes patients: retrospective data analysis [abstract]. Value Health. 2003;6:328. 18. Spoelstra JA, Stolk RP, Heerdink ER, et al. Refill compliance in type 2 diabetes mellitus: a predictor of switching to insulin therapy? Pharmacoepidemiol Drug Saf. 2003;12:121–127. 19. Venturini F, Nichol MB, Sung JC, Bailey KL, Cody M, McCombs JS. Compliance with sulfonylureas in a health maintenance organization: a pharmacy record– based study. Ann Pharmacother. 1999;33:281– 288. 20. Dezii CM, Kawabata H, Tran M. Effects of once-daily and twice-daily dosing on adherence with prescribed glipizide oral therapy for type 2 diabetes. South Med J. 2002;95:68 –71. 21. 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. 22. Grant RW, Devita NG, Singer DE, Meigs JB. Polypharmacy and medication adherence in patients with type 2 diabetes. Diabetes Care. 2003;26:1408 –1412. 23. Larsen J, Vaccheri A, Andersen M, Montanaro N, Bergman U. Lack of adherence to lipid-lowering drug treatment: a comparison of utilization patterns in defined populations in Funen, Denmark and Bologna, Italy. Br J Clin Pharmacol. 2000;49:463– 471. 24. Collins R, Armitage J, Parish S, et al, for the Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–2016. 25. Brown JB, Nichols GA, 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;21:1045–1057. 26. Schillinger D, Grumbach K, Piette J, et al. Association of health literacy with diabetes outcomes. JAMA. 2002;288:475– 482. 27. Schillinger D, Piette JD, Grumbach K, et al. Closing the loop: physician communication with diabetic patients who have low health literacy. Arch Intern Med. 2003;163:83–90. 28. Piette JD, Schillinger D, Potter MB, Heisler M. Dimensions of patient– provider communication and diabetes self-care in an ethnically diverse population. J Gen Intern Med. 2003;18:624 – 633. 29. Piette JD. Moving from research to action: how we can help patients with low health literacy problems. Paper presented at the 64th Annual Scientific Sessions of the American Diabetes Association; June 4 – 8, 2004; Orlando, Florida. 30. Ciechanowski PS, Katon WJ, Russo JE, Walker EA. The patient– provider relationship: attachment theory and adherence to treatment in diabetes. Am J Psychiatry. 2001;158:29 –35. 31. Harris LE, Luft FC, Rudy DW, Tierney WM. Correlates of health care satisfaction in inner-city patients with hypertension and chronic renal insufficiency. Soc Sci Med. 1995;41:1639 –1645. 32. Alazri MH, Neal RD. The association between satisfaction with services provided in primary care and outcomes in type 2 diabetes mellitus. Diabet Med. 2003;20:486 – 490. 33. Kerr EA, Smith DM, Kaplan SH, Hayward RA. The association between three different measures of health status and satisfaction among patients with diabetes. Med Care Res Rev. 2003;60:158 –177. 34. Geelhoed-Duijvestijn PHLM, Peyrot M, Mathews DR, et al. Physician resistance to prescribing insulin: an international study [abstract]. Diabetologia 2003;46(suppl 2):A274 –A275. 35. Peyrot M, Mathews DR, Snoek FJ, et al. An international study of psychological resistance to insulin use among persons with diabetes [abstract]. Diabetologia 2003;46(suppl 2):A89. Abstract. 36. Peyrot M, Rubin R, Siminerio L. Physician and nurse use of psychosocial strategies and referrals in diabetes [abstract]. Diabetes 2002; 51(suppl 2):A446. 37. Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care. 2000;23:934 –942.
34S 38. de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med. 2001;63:619 – 630. 39. Clouse RE, Lustman PJ, Freedland KE, Griffith LS, McGill JB, Carney RM. Depression and coronary heart disease in women with diabetes. Psychosom Med. 2003;65:376 –383. 40. Egede LE, Zheng D, Simpson K. Comorbid depression is associated with increased health care use and expenditures in individuals with diabetes. Diabetes Care. 2002;25:464 – 470. 41. Polonsky WH, Anderson BJ, Lohrer PA, et al. Assessment of diabetesrelated distress. Diabetes Care. 1995;18:754 –760. 42. Rubin RR, Ciechanowski PS, Egede LE, Lin EHB, Lustman PJ. Recognizing and treating depression in patients with diabetes. Curr Diab Rep. 2004;4:119 –125. 43. Spitzer RL, Kroenke K, Williams JB, et al, for the Patient Health Questionnaire Primary Care Study Group. Validation and utility of a self-report version of the Primary Care Evaluation of Mental Disorders (PRIME-MD): the Patient Health Questionnaire (PHQ) Primary Care Study. JAMA. 1999;282:1737–1744. 44. Beck AT, Beamesderfer A. Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry. 1974;7:151–169. 45. Radloff LS. The Center for Epidemiologic Studies Depression Scale (CES-D): a self-report depression scale for research in the general population. Applied Psychological Measurement. 1977;1:385– 401. 46. Lustman PJ, Griffith LS, Clouse RE, et al. Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med. 1997;59:241–250.
The American Journal of Medicine, Vol 118 (5A), May 2005 47. Lustman PJ, Freedland KE, Griffith LS, Clouse RE. Fluoxetine for depression in diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2000;23:618 – 623. 48. Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE. Cognitive behavior therapy for depression in type 2 diabetes mellitus: a randomized, controlled trial. Ann Intern Med. 1998;129:613– 621. 49. Rubin RR, Perot M. Was Willis right? Thoughts on the interaction of depression and diabetes. Diabetes Metab Res Rev. 2002;18:173–175. 50. Piette JD, Weinberger M, McPhee SJ, Crapo LA, Kraemer FB. Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes? Am J Med. 2000; 108:20 –27. 51. Haynes RB, McDonald H, Garg AX, Montague P. Interventions for helping patients to follow prescriptions for medications. The Cochrane Library. 2003;4:1–50. 52. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Press; 1994:327. 53. Norris SL, Lau J, Smith SJ, Schmid CH, Engelgau MM. Self-management education for adults with type 2 diabetes: a meta-analysis of the effect on glycemic control. Diabetes Care. 2002;25:1159 –1171. 54. Peyrot M, Rubin RR. Modeling the effect of diabetes education on glycemic control. Diabetes Educ. 1994;20:143–148. 55. Rubin RR, Peyrot M, Saudek CD. Differential effect of diabetes education on self-regulation and life-style behaviors. Diabetes Care. 1991;14:335–338.
Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus Richard R. Rubin, PhD Departments of Medicine and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. KEYWORDS: Adherence; Pharmacologic therapy; Type 2 diabetes mellitus
Many patients who have type 2 diabetes mellitus (DM) require several different medications. Although these agents can substantially reduce diabetes-related morbidity and mortality, the extent of treatment benefits may be limited by a lack of treatment adherence. Unfortunately, little information is available on treatment adherence in patients with type 2 DM. Available data indicate substantial opportunity for improving clinical outcomes through improved treatment adherence. Factors that appear to influence adherence include the patient’s comprehension of the treatment regimen and its benefits, adverse effects, medication costs, and regimen complexity, as well as the patient’s emotional well-being. Outcomes research emphasizes the importance of effective patient–provider communication in overcoming some of the barriers to adherence. This article offers specific suggestions for improving adherence in patients with type 2 DM seen in general clinical practice. © 2005 Elsevier Inc. All rights reserved.
Many patients who have type 2 diabetes mellitus (DM) require several different medications. In a US survey of adults treated with glucose-lowering medication, 50% reported using ⱖ7 medications in their prescribed treatment regimen, including ⱖ2 glucose-lowering agents.1 The reason for the large numbers of prescriptions is clear: evidence shows that tight control of blood glucose, cholesterol, and blood pressure helps these patients stay healthy. In fact, the potential for better outcomes has never been greater for those who adhere to their regimens. The number of pharmacologic agents prescribed and the number of patients who need them are growing at a disturbingly fast pace due to the type 2 DM epidemic. Improved treatment adherence may close the gap between potential treatment benefits and the benefits patients actually receive.1-4 However, despite the importance of adherence for patients
Requests for reprints should be addressed to Richard R. Rubin, PhD, Johns Hopkins University School of Medicine, 500 West University Parkway, Baltimore, Maryland 21210. E-mail address: [email protected].
0002-9343/$ -see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2005.04.012
with type 2 DM, surprisingly little is known about the problems related to medication adherence in this disease state.5 This article discusses what is known about estimated adherence rates, factors affecting adherence, and interventions to facilitate adherence in the type 2 DM patient population.
Adherence rates In 1995, Mason and colleagues6 and Matsuyama and coworkers7 studied 47 patients with type 2 DM. They assessed treatment adherence using medication containers with electronic monitoring systems that counted the number of times a patient opened them. Assessment of medication adherence by provider, patient self-report, and pill counts was less reliable for explaining metabolic control than was the electronic monitoring system. Since that time, ⬃20 studies of treatment adherence in patients with type 2 DM have been reported, with most published in the past few years (Table 1).8-25 These studies are inclusive of several that used protocols requiring electronic monitoring8-10 and retrospective studies that used
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Treatment adherence in patients with type 2 diabetes mellitus
Type of medication
No. of Studies
Adherence Rate (%)
Oral blood glucose–lowering Insulin Blood pressure, cholesterol-lowering
25 2 3
65–85* 60–80 75–90
*The adherence rate was lower (36%–54%) for certain agents, regimens, and populations.
Table 2
Factors influencing treatment adherence
Factor
Critical Issues
Comprehension of regimen
● ● ● ● ● ● ● ● ● ● ●
Perception of benefits
Side effects Medication costs Regimen complexity Emotional well-being
Health literacy Clinician’s use of jargon Closing the communication loop Medications provide limited symptom relief Personally meaningful long-term benefit critical Role of clinician’s attitudes toward medication Vary by agent Rarely discussed Rarely discussed Adherence to timing may be greatly affected Benefits of treating depression, diabetes distress
large prescription databases maintained by pharmacy benefits managers, health maintenance organizations, Medicaid, or national health services.11-14 Most of these studies reported that adherence to oral blood glucose–lowering therapy ranged from 65% to 85%,2,6-12,14-19 although a few reported lower rates (36%–54%) for certain patient populations (eg, Medicaid recipients)13 and regimens (those requiring more frequent dosing).16,20,21 Due to the small number of studies, differences in study designs, and variations in the findings, little is known specifically about adherence to oral blood glucose–lowering medications in patients with type 2 DM. Even less is known about adherence to insulin, blood pressure–lowering, and lipid-lowering therapies in these patients. The few studies that are available suggest that self-reported adherence to blood pressure–lowering and lipid-lowering medication regimens may be a bit higher than adherence to oral glucose– lowering regimens,22-24 whereas adherence to insulin regimens may be slightly lower.17,25 Whether adherence rates are high or low, there is substantial room for improvement.
Factors influencing adherence Comprehension of the treatment regimen Of the factors that may affect treatment adherence (Table 2), perhaps the most common and most overlooked is
patients’ comprehension of the treatment regimen, which clinicians often overestimate. Schillinger and coworkers26 studied 408 English-speaking and Spanish-speaking patients in public hospitals and found that ⬎50% of both groups had limited health literacy, defined as comprehension of common medical terms or concepts (eg, stable blood pressure) and/or instructions, such as for dosing (eg, take this medication 4 times a day). Lack of patient comprehension often goes unrecognized by physicians, who rarely verify patients’ recall and comprehension of their treatment regimens. In another study by Schillinger’s group,27 office visits of patients with type 2 DM were audiotaped to determine how often physicians introduced a new concept (e.g., a treatment-adjustment recommendation) and how often they assessed patients’ recall and comprehension of that concept. In 82% of office visits, ⱖ1 new concept was introduced, at least half of which concerned a treatment adjustment. Physicians assessed patient recall and comprehension in only 12% of these situations. The mean duration of visits in which recall and comprehension were assessed was similar to that of visits in which they were not. Furthermore, patients whose physicians assessed recall and comprehension had lower glycosylated hemoglobin (Hb) A1c concentrations than those patients whose physicians did not assess recall. This study demonstrates the need for and impact of effective physician–patient communication regarding treatment regimens.
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For patients with type 2 DM, health literacy also includes understanding instructions for self-care (including treatment adherence)28 and glycemic control, as well as concepts such as patient outcomes and medication costs.28,29 Ensuring effective communication means clarifying and restating messages until a patient’s recall and comprehension are verified. A study conducted in 2001 by Ciechanowski and colleagues30 found that patients who rated the communication provided by their physicians as good were significantly more adherent to oral blood glucose–lowering regimens (P ⬍0.05) and to recommendations for self-monitoring blood glucose (P ⬍0.01) than those patients who rated their physicians as poor communicators. Others found similar advantages in treatment satisfaction,27,31 glycemic control,32 and health status33 among patients reporting good communication with their healthcare providers.
Perception of treatment benefits Effective provider–patient communication can help clinicians address other factors that influence treatment adherence, including patients’ perceptions of the potential benefits of adherence. A study by Grant and associates22 emphasized that patients are more likely to adhere to treatments they perceive as helpful in alleviating their symptoms than to those they do not. Because hypertension and dyslipidemia in some patients with type 2 DM are not associated with any recognizable signs or symptoms, care must be taken by physicians to communicate effectively to patients who may not be aware of the potential benefits of treating an asymptomatic condition. Additionally, many patients do not recognize the symptoms of hyperglycemia. Clinicians can help patients understand the short-term benefits of glycemic control (e.g., increased energy, better quality sleep, fewer school days or workdays missed) and remind patients that using medication as prescribed contributes to attaining these benefits. Patients’ perceptions of treatment benefits are also influenced by clinicians’ attitudes and practices regarding antidiabetic medications. In a multinational survey of patients with type 2 DM and their physicians,34 59% and 43% of physicians indicated that they preferred to delay insulin and oral antihyperglycemia therapies, respectively, until they were essential. In addition, when asked how often they told patients they will have to start insulin if they do not follow medical advice, 57% of physicians responded either “always” or “often.” Given these physicians’ attitudes and practices, it may not be surprising that many patients surveyed had negative attitudes and, consequently, were not using insulin.35 For example, only 23% of these patients reported believing that insulin therapy would help them manage their DM, and 48% reported believing that being prescribed insulin therapy was an indication that they had failed to follow their treatment regimen correctly. The influence of physicians’ attitudes and behaviors on patient treatment adherence requires further investigation. In the meantime, physi-
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cians should recognize the impact their own attitudes and behaviors may have on patients and take the time to communicate effectively with their patients about the long-term benefits of prescribed medications.
Regimen complexity Many patients with type 2 DM are prescribed complex treatment regimens to help them achieve glycemic goals. Several retrospective database studies have shown that rates of adherence to polytherapy regimens were 10% to 20% lower than those for monotherapy regimens.13,16,21 Paes and colleagues8 used electronic monitoring to compare adherence to medications dosed once, twice, or thrice daily. To determine whether agents were taken at the prescribed times, the monitoring system tracked not only how often the medication containers were opened but also precisely when. The adherence rate for once-daily dosing was 79%; those for 2 and 3 times daily dosing decreased to 66% and 38%, respectively. Furthermore, medications were taken at the prescribed times in 77% of cases of once-daily dosing; the rate fell to 41% and 5%, respectively, for dosing 2 and 3 times daily. These findings suggest that prescribing medications that require fewer doses can increase medication adherence. However, physicians should bear in mind another finding of this study: ⬎33% of patients used more medication than prescribed, and these were primarily patients whose medications were dosed once a day. Patients must fully comprehend the prescribed regimen, and must have a dependable system for monitoring medicine that has been taken.
Perceived adverse effects Adverse effects (AEs) (i.e., hypoglycemia, weight gain) as well as agent tolerability, drug– drug interactions and complicated drug regimens lead some patients to use medications prescribed for the treatment of type 2 DM, hypertension, and high cholesterol levels either less often than prescribed or not at all. In a study by Boccuzzi and colleagues,11 after 12 months of metformin therapy 60% of patients were still adherent to their medication regimen, whereas 12-month persistence rates for sulfonylureas, repaglinide, and ␣-glucosidase inhibitors were lower (56%, 48%, and 31%, respectively). In a study of 128 patients using ⱖ3 medications concurrently, 21% were not perfectly adherent to their regimens.22 Of these, ⬎70% were perfectly adherent to all but 1 agent. AEs were the most common reason for lack of adherence, were fairly serious, and were long lasting (⬎30 days). However, AEs were rarely addressed in office visits: ⬍25% of patients mentioned them to their healthcare providers. Clearly, patients should be asked about AEs, and their treatment should be adjusted accordingly.
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Medication costs
that they received treatment for these problems. Another report estimated that only 25% of patients with type 2 DM who experienced depression received adequate treatment for it.42 Identifying and treating depression and DM-related emotional distress can contribute to improved treatment adherence and other positive outcomes. Physicians can identify patients at risk for distress or depression by regularly discussing symptoms with the patient or by using a validated screening questionnaire, such as the Patient Health Questionnaire–9,43 the Beck Depression Inventory,44 or the Center for Epidemiological Studies Depression Scale.45 Furthermore, effective treatment of distress or depression has been associated with improved metabolic outcomes. Several small, short-term (8- to 10-week), randomized clinical trials have shown that treatments for depression effective in the general population were also effective in patients with type 2 DM. In separate studies, the active treatments nortriptyline,46 fluoxetine,47 and cognitive-behavioral therapy (CBT) plus DM education48 were compared with controls (placebo and DM education alone, respectively); in each study, the severity of depressive symptoms was significantly reduced with the active treatment compared with controls (P ⫽ 0.03, P ⬍0.01, P ⬍0.001, respectively). Nortriptyline was not statistically more effective than placebo in reducing HbA1c levels in depressed patients (P ⫽ 0.5), but there was a trend toward greater reduction in HbA1c in patients treated with fluoxetine, compared with those taking placebo (P ⫽ 0.13), and HbA1c levels were significantly lower at follow-up in patients receiving CBT plus education than in patients receiving education alone (P ⫽ 0.03). Effective treatment of distress and depression could lead to improved glycemic control directly49 or by increasing motivation and changing behavior, including increasing treatment adherence.
Medication costs can affect adherence. In a US survey of adults with type 2 DM receiving blood glucose–lowering therapy, 11% indicated that they had limited their medications in the past year due to cost, with 7% having cut back in the past month.1 Predictably, patients with little or no prescription-drug coverage had more difficulty affording medications than those whose prescriptions were mostly or completely covered. Provider–patient communication concerning cost seems limited. Of respondents who indicated medication cutbacks, only 32% reported informing their providers of the cutback, and 37% said they had not discussed medication costs with their providers. Furthermore, clinicians do not seem to be doing everything possible to prevent cost as a barrier to adherence. About 70% of patients indicated that their providers had not raised the issue of medication costs, and only ⬃10% reported being given information on sources of lowcost medications or financial assistance programs. A similar proportion of patients (⬃10%) reported that their providers had prescribed fewer medications to decrease out-of-pocket expenses. The reasons patients provided for not discussing cost with their clinicians point toward opportunities for improvement: 50% did not believe their healthcare provider could help with costs, 39% did not believe cost was important enough to mention, 35% felt embarrassed, and 30% felt there was not enough time during their visits to talk about it. Clinicians should ask their patients about cost-related problems with treatment adherence and make it clear that cost is an important issue, and should not cause embarrassment, given the high cost of medications and other necessities. Clinicians should also offer information on sources of inexpensive medications and financial assistance programs and make treatment adjustments as appropriate to minimize costs.
Emotional well-being In a study by Peyrot and associates,36 investigators found that almost 70% of clinicians responding to the Diabetes Attitudes Wishes and Needs (DAWN) survey reported that psychological problems (including stress and depression) affected treatment adherence in their patients with type 2 DM. Clinicians seem to recognize that depression and DMrelated emotional distress (eg, frustration with symptoms, disease management) can decrease concentration, energy, self-sufficiency, motivation, and self-care while increasing blood glucose levels, healthcare costs, and the risk for diabetic complications.12,36-41 Unfortunately, although clinicians recognize the impact of psychological problems on medical outcomes, patients with type 2 DM rarely receive psychological treatment. In the DAWN survey, almost 50%of patients reported specific psychological problems and poor psychological well-being, but only 10% indicated
Methods to improve adherence Verifying recall and comprehension Several methods have been used to improve treatment adherence (Table 3), including verifying recall and comprehension. Physicians can verify patients’ recall and comprehension of treatment regimens by asking patients to restate dosing instructions and recommended treatment changes. Physicians should ask questions not to “test” the patient, but in a way that indicates that they are simply checking to ensure they have communicated clearly (e.g., “Just to be sure I’ve been clear, tell me your understanding of when you should take the medication.”). Using pictures of medication facilitates recall and comprehension in some patients (e.g., “Just to be clear, let’s review the instructions for all your medications. Here are pictures of the pills you should take; tell me when you should take this one.”).
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Adherence to Pharmacologic Therapy in Patients with Type 2 Diabetes Mellitus Table 3
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Interventions to facilitate treatment adherence
Goal/target
Intervention
Enhance regimen recall/ comprehension
● Verify patient’s understanding while in the office ● Use visual aids ● Clarify limited symptom relief ● Find meaningful long-term benefits ● Discuss and monitor ● Make adjustments ● Discuss and monitor ● Change regimen when appropriate ● Monitor ● Change regimen when appropriate ● Screen for depression ● Treat depressed patients or refer ● Screen for diabetes-related distress ● Facilitate problem solving ● Refer for diabetes education
Enhance perceived benefits of regimen
Minimize adverse effects Minimize costs
Minimize regimen complexity Facilitate emotional well-being
Clarifying potential treatment benefits Patients should be helped to understand that they will not feel the benefits of some medications that are prescribed to protect future health. The clinician could say, “Can you feel the benefits of your blood pressure and cholesterol pills? If you are like most people, the answer is no. But those pills help keep your blood pressure and cholesterol level where they belong; reduce your risk for a heart attack or stroke; and help you live a longer, healthier life. You take these pills because you want to stay healthy in the future. What is your biggest reason for wanting to stay healthy in the future?” Some people feel the short-term benefits of glucoselowering medication and should be encouraged to identify these benefits. A clinician could say, “When they take their medication as prescribed, some people notice their blood sugar control improves. Have you noticed that? If so, does better control change anything in your life? Some people say they have more energy, sleep better, are sick less often, or miss fewer days of work. Are any of those things true for you?”
Simplifying regimens Clinicians can ask questions to identify any adherence problems related to regimen complexity: “Of all your medications, which are you most likely to skip or forget, and when? How often do you skip or forget them? Why do you skip them?” Clinicians can offer a simpler treatment regi-
men (fewer medications or less frequent dosing) or suggest systems to help the patient remember to take medications on time and keep track of what was taken.
Electronic monitoring In a study by Matsuyama and colleagues,7 physicians and pharmacists used data from electronic monitoring to help them make appropriate medication adjustments. These data were most helpful in determining whether hyperglycemia was related to an inadequate prescription or to missed doses. In a randomized controlled trial by Rosen and associates,10 17 patients in the intervention group engaged in a structured dialogue with a healthcare provider about daily medication dosing using the patients’ own electronic monitoring devices. This intervention led to improved adherence in this group compared with controls (n ⫽ 16), who received no intervention, although the change in HbA1c concentration was statistically similar between the 2 groups. Another trial by Piette and colleagues50 evaluated the effect of telephone calls from a physician’s office on adherence and outcomes. Twenty-eight patients in an intervention group received biweekly automated calls that assessed health status and provided self-care education. A nurse made follow-up calls to patients who reported problems. The intervention group averaged 1.4 completed automated calls per month, and the mean duration of contact with a nurse was 6 minutes per month. After 12 months, compared with a group receiving usual care, the intervention group reported better treatment adherence (all P ⱕ0.03), fewer
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DM symptoms (P ⬍0.0001), and lower (0.3%) HbA1c concentrations. Although electronic monitoring and automated telephone assessment and support systems generally are not available, elements of these successful strategies that will improve patient outcomes can be incorporated into general clinical practice.
for and treat depression or refer these patients for treatment. The following 9 symptoms are characteristic of depression: (1) depressed mood, (2) anhedonia (loss of interest and pleasure), (3) change in sleep, (4) change in appetite or weight, (5) low energy, (6) psychomotor agitation or retardation, (7) poor concentration, (8) low self-esteem or guilt, and (9) recurrent thoughts of death. At least 1 of the 2 cardinal symptoms— depressed mood and anhedonia— must be present for a diagnosis of major depression as defined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.52 A patient could have depression but not mention depressed mood; anhedonia might be the primary symptom. Clinicians can screen for depression by asking questions about depressed mood and anhedonia— e.g., “During the past 2 weeks, have you felt down, depressed, or hopeless? Have you lost interest or pleasure in doing things you once enjoyed?” If the answer to one or both questions is affirmative, the clinician then should ask about the remaining 7 symptoms of depression. A variety of validated self-report questionnaires for depression screening also are available.43-45 Most patients can complete any of the widely used depression screeners in ⬍5 minutes, and the results can be obtained in ⬍2 minutes, so the results should be available to discuss at the same visit. CBT and antidepressants are effective treatments for depression in patients with DM. Although most patients experience a full response to antidepressant medication within 6 weeks,42 some require 12 weeks, so patients should be prepared for the possibility of delayed benefits to avoid disappointment and premature discontinuation of the medication. Patients should be carefully monitored for remission of depressive symptoms and for AEs. Insomnia, agitation, and loss of libido are common in patients receiving treatment with a selective serotonin reuptake inhibitor or related medications, especially fluoxetine and paroxetine. Techniques for managing AEs include starting at a low dose, adding an agent to manage the AE, or switching agents. Referral to a mental healthcare professional is appropriate if the diagnosis is in doubt, if the patient has a complicated psychiatric history, or if the patient does not respond to antidepressant medication or experiences ⱖ1 serious AE. Patients who do not have depression may still experience diabetes-related emotional distress. Clinicians should identify these patients and formulate treatment interventions to address the sources of distress. The Problem Areas in Diabetes survey, developed by Polonsky and colleagues,41 can help clinicians assess a patient’s overall level of DM-related emotional distress as well as its specific sources (e.g., sources that may represent barriers to treatment adherence).
Minimizing costs To help minimize cost-related adherence problems, clinicians should know the approximate out-of-pocket costs of various agents, as well as sources of low-cost medications and financial-assistance programs. They should ask directly about cost-related adherence problems, just as they do about AEs: “The medication I just prescribed will cost you about $50 a month in co-payments. Will that be a problem for you?” If the answer is yes, the physician can explore further. Difficulty affording medications should be monitored consistently. For example, a clinician might say, “Medication costs are a real problem for many people. Are you having trouble paying for any of your medications? If you are, what are you doing about it? Have you cut back on any of your medications? If so, which ones, and by how much? Have you cut back on other things to pay for your medicine?” Clinicians should also offer to change the regimen if appropriate, and provide information on sources of low-cost medications or financial assistance.
Discussing adverse effects Clinicians can minimize barriers to medication adherence by titrating doses and discussing potential AEs with their patients. The nature and course of common AEs should be described. Patients should also be strongly encouraged to call the clinician if interactions or AEs arise. Making a correction 1 or 2 weeks after the original adjustment is preferable to making it at the patient’s next visit several months later. This method also reinforces the provider– patient relationship and helps ensure that patients will return for follow-up visits. Follow-up visits are the most effective way to improve treatment adherence; many patients who are not seen regularly are unlikely to adhere to their treatment regimens.51 Medications should be monitored at each visit with some simple questions: “How are things going with your medication? Are you having any problems?” If a patient does not mention any, he or she should be asked about specific AEs that commonly occur with that agent. In fact, clinicians should regularly ask about AEs for all medications.
Minimizing depression or diabetes-related emotional distress Depression and diabetes-related emotional distress require treatment because of their substantial impact on treatment adherence and patient outcomes. Clinicians can screen
Summary Education is a useful resource for addressing all barriers to treatment adherence in patients with type 2 DM. Studies
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Adherence to Pharmacologic Therapy in Patients with Type 2 Diabetes Mellitus
show that self-management education improves patients’ understanding, confidence, and level of self-care, and leads to improvement in self-care behavior, glycemic control, and good patient outcomes.53-55 Working with patients to enhance treatment adherence helps to strengthen and maintain a collaborative patient– provider relationship. Patients who are satisfied with their provider–patient relationship are more likely to return for follow-up, which is the most powerful predictor of treatment adherence and other self-care behaviors.
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