Elsevier

Clinical Therapeutics

Volume 33, Issue 1, January 2011, Pages 74-109
Clinical Therapeutics

Pharmaceutical economics & health policy
Review article
A Review of Diabetes Treatment Adherence and the Association with Clinical and Economic Outcomes

https://doi.org/10.1016/j.clinthera.2011.01.019Get rights and content

Abstract

Background

The benefits of drug therapy to diabetic patients in terms of glycemic control, microvascular complications, cardiovascular event risk, mortality, and quality of life have been well established by clinical trial data. However, it has been a challenge to quantify the relationship between adherence and outcomes such as glycemic control, disease-related events, hospitalizations, cost, and quality of life.

Objective

This article provides a comprehensive summary of empirical studies that examine the associations between adherence and glycemic control, health care utilization, quality of life, and mortality in patients with diabetes. It is intended to provide a framework for researchers interested in conducting studies to improve their understanding of the value of medication adherence for patients with diabetes.

Methods

Relevant published articles were identified through searches of the National Center for Biotechnology PubMed database. Medical subject heading (MESH) terms diabetes mellitus, hypoglycemic agents, and insulin, were each combined with the MESH term medication adherence and with the subheadings economics, prevention and control, psychology, statistics and numerical data, therapy, adverse effects, therapeutic use, and administration and dosage, where available. Studies were included if they met the following criteria: (1) analyzed empirical data on some measure of patient adherence to diabetes pharmacotherapy; (2) described methods for measuring patient adherence; (3) evaluated economic, clinical, or humanistic outcomes related to diabetes; and (4) had as a goal of the research to evaluate the link between patient adherence and outcomes (as a primary or secondary objective). The data from the articles meeting these criteria were then abstracted, including mention of the specific interventions being compared, specific methods for measuring adherence, outcomes compared between adherent and nonadherent patients and how these outcomes were measured, and information on variables that were adjusted for in predictive and causal multivariable models.

Results

A total of 37 articles that met all 4 criteria in this review underwent data extraction. Of these studies, 22 (59%) used objective measures to assess adherence, with 1 study using pill counts to assess adherence and 21 using either pharmacy claims or similar refill records to assess refill behavior. The remaining 15 (41%) studies used a wide variety of subjective patient-reported adherence assessments. The majority (13/23 [57%]) of the glycemic control studies reported that improved adherence was associated with better glycemic control. The ability to draw a distinction between adherence and glycemic control tended to occur more frequently [7/9 (78%)] among studies that characterized adherence in terms of prescription refills compared with studies that used various constructs for patient-reported adherence measures.

Conclusions

Based on the literature, better adherence was found to be associated with improved glycemic control and decreased health care resource utilization. There was no consistent association between improved adherence and decreased health care costs. Little data were available on the association between adherence and quality of life.

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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