Pharmaceutical economics & health policyReview articleA Review of Diabetes Treatment Adherence and the Association with Clinical and Economic Outcomes
Introduction
Diabetes is a chronic, progressive metabolic disorder characterized by the body's inability to maintain a normal condition of glucose homeostasis. The long-term manifestations of diabetes contribute to its status as a leading cause of premature illness and mortality worldwide.1 In the United States, diabetes affects 23.6 million people (7.8% of the population), with a prevalence that appears to be increasing.2 The Centers for Disease Control and Prevention estimate that the number of Americans with diabetes will more than double—to 48 million—by 2050.3 Long-term glycemic control is fundamental to the management of diabetes and has been shown to reduce both microvascular and macrovascular complications. According to a joint consensus guideline from the American Diabetes Association and the European Association for the Study of Diabetes, initial pharmacotherapy for diabetes depends on a patient's diagnosis: type I diabetes is treated with exogenous insulin, whereas type II diabetes is treated initially with an oral antihyperglycemic agent, such as metformin, with additional agents being added as needed, including sulfonylureas, insulin, thiazolidinediones, and glucagon-like peptide 1 (GLP-1) agonists.4 However, despite adequate diagnosis and medical care, patients often fail to derive the optimal clinical benefit of drug therapy because of medication nonadherence.5 Nonadherence may contribute to a considerable degree of undue glycemic burden and resulting morbidity and mortality for patients being treated for diabetes.
The term adherence is an umbrella term that encompasses both the concepts of compliance and persistence. Medication compliance has been defined by the International Society for Pharmacoeconomics and Outcomes Research as the “extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen.”6 Persistence is defined as “the duration of time from initiation to discontinuation of therapy.”6
Nonadherence with prescribed medications is a problem of enormous magnitude. Across all diseases, the overall economic impact of nonadherence in the United States has been estimated at $100 billion.7 In diabetes, nonadherence rates for oral antihyperglycemic medications among patients who received at least 1 fill range from 36% to 93%.5
The benefits of drug therapy in terms of improved glycemic control,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 microvascular complications,13 cardiovascular event risk,13 mortality,13 and quality of life25 have been well established by clinical trial data. Although it seems intuitive that improved adherence influences positive health outcomes in diabetes, in reality it can be challenging to quantify the relationship between adherence and outcomes such as glycemic control, disease-related events, hospitalizations, cost, and quality of life. To date, at least 1 systematic review has examined overall patient adherence in diabetes,5 and another has explored the economic consequences that may result from nonadherence with diabetes medications.26 These studies reported that adherence is poor among many patients5 and that studies linking costs to level of adherence are generally poor in quality.26 This review builds on previous works by providing an updated comprehensive summary of empirical studies that examine the associations between adherence and glycemic control (A1C), health care utilization, quality of life, and mortality in patients with diabetes. The goal of this work is to improve our understanding of the value of medication adherence for patients with diabetes.
Section snippets
Methods
We searched PubMed (http://www.ncbi.nlm.nih.gov/sites/entrez/) of the National Center for Biotechnology Information for publications that linked patient adherence to outcomes related to diabetes, including economic, clinical, and humanistic outcomes. All observational study design types were considered eligible, including retrospective and prospective studies with cohort, cross-sectional, and case-control designs; experimental studies were excluded because patient adherence in clinical trials
Articles
The search returned 2370 articles, of which 834 were excluded before stage I screening either because they were not in English (283), they had no abstract available (619), or they were readily identifiable as review articles, editorials, or letters to the editor (285). Reviewers then screened abstracts for 1536 articles, from which 1127 were excluded because it was clear that they did not meet all 3 stage I criteria: assessing patient adherence to diabetes pharmacotherapy (1052), describing the
Discussion
In diabetes, as with other chronic conditions, successful avoidance of the long-term clinical manifestations of disease requires a lifetime of treatment with medication. Although randomized clinical trials are a cornerstone of clinical decision making, adherence to medication therapy is a key factor in the translation of clinical trial efficacy to real-world effectiveness. To this end, both clinicians and health policy decision makers can benefit from a robust understanding of the issues
Conclusions
This review found that researchers use a variety of methods to quantify adherence and have described its relationship to a variety of clinical, economic, and humanistic outcomes. We found that better adherence tends to be associated with improved glycemic control. In addition, better adherence tends to be associated with decreased utilization of health care services, but the association between adherence and health care costs was mixed across studies, most likely because of the increase in drug
Acknowledgments
This study was funded by Novo Nordisk. Drs. Asche and LaFleur are faculty members of the University of Utah College of Pharmacy. Dr. Conner is an employee of Novo Nordisk. The authors gratefully acknowledge the assistance of Dr. Mark Aargren (Novo Nordisk), Ms. CarrieAnn McBeth, and Mr. Blaine Osborne in compiling the research results required for this article.
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