A Systematic Review of Adherence With Medications for Diabetes JOYCE A. CRAMER OBJECTIVE — The purpose of this study was to determine the extent to which patients omit doses of medications prescribed for diabetes. RESEARCH DESIGN AND METHODS — A literature search (1966 –2003) was per- formed to identify reports with quantitative data on adherence with oral hypoglycemic agents (OHAs) and insulin and correlations between adherence rates and glycemic control. Adequate documentation of adherence was found in 15 retrospective studies of OHA prescription refill rates, 5 prospective electronic monitoring OHA studies, and 3 retrospective insulin studies. RESULTS — Retrospective analyses showed that adherence to OHA therapy ranged from 36 to 93% in patients remaining on treatment for 6 –24 months. Prospective electronic monitoring studies documented that patients took 67– 85% of OHA doses as prescribed. Electronic moni- toring identified poor compliers for interventions that improved adherence (61–79%; P  0.05). Young patients filled prescriptions for one-third of prescribed insulin doses. Insulin adherence among patients with type 2 diabetes was 62– 64%. CONCLUSIONS — This review confirms that many patients for whom diabetes medication was prescribed were poor compliers with treatment, including both OHAs and insulin. However, electronic monitoring systems were useful in improving adherence for individual patients. Sim- ilar electronic monitoring systems for insulin administration could help healthcare providers determine patients needing additional support. Diabetes Care 27:1218 –1224, 2004 D iabetes is a complex disorder that requires constant attention to diet, exercise, glucose monitoring, and medication to achieve good glycemic con- trol. Glasgow (1) conceptualized the com- plexity of diabetes regimens, creating a model linking disease management and health outcomes with interactions be- tween patients and their healthcare pro- viders. Factors contributing to optimum disease management included age, com- plexity of treatment, duration of disease, depression, and psychosocial issues (1). Although a variety of terms have been used to describe these self-management or self-care activities (e.g., adherence, compliance, concordance, fidelity, persis- tence), compliance is the default medical term used in the literature (MEDLINE) to describe medication dosing (2). However, the World Health Organization has pro- moted the term “adherence” for use in chronic disorders as “the extent to which a person’s behavior—taking medication, following diet, and/or executing lifestyle changes— corresponds with agreed rec- ommendations from a health care pro- vider” (3). The incidence of type 2 diabetes is rapidly increasing, largely in older, over- weight patients who have concomitant cardiovascular risks (4). However, health care systems often do not have adequate resources to provide support to individu- als with chronic diseases. Problems with poor self-management of drug therapy may exacerbate the burden of diabetes. Several studies suggest that a large proportion of people with diabetes have difficulty managing their medication reg- imens (oral hypoglycemic agents [OHAs] and insulin) as well as other aspects of self-management (1,5,6). Whereas some studies that have assessed adherence among young people with type 1 diabetes (6,7), little is known about adherence to insulin regimens in patients with type 2 diabetes. This systematic review was under- taken 1) to assess the extent of poor ad- herence and persistence with OHAs and insulin and 2) to link adherence rates with glycemic control. RESEARCH DESIGN AND METHODS Literature search A systematic literature search was con- ducted to identify articles containing in- formation on the rate of adherence or persistence with OHAs or insulin. Ab- stracts captured by the systematic litera- ture search of MEDLINE (1966 to April 2003), Current Contents (1993 to April 2003), Health & Psychosocial Instru- ments (1985–2003), and Cochrane Col- laborative databases were first screened against the protocol inclusion criteria. The Level 1 screen identified papers re- lated to the main topic of interest. Ab- stracts passing the Level 1 screen were then retrieved for screening against the inclusion criteria (Level 2 screen). Full ar- ticles meeting the inclusion criteria were reviewed in detail (Level 3 screen). Inclusion criteria Papers were included in this review if 1)a dosing regimen was evaluated and medi- cation adherence or persistence rates were reported and 2) study design and methods for calculation of adherence were described. The papers must have in- cluded details of the methods used to de- termine adherence with a hypoglycemic agent (e.g., self-report, physician/nurse estimate, tablet count, prescription refill, ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Address correspondence and reprint requests to Joyce A. Cramer, Yale University School of Medicine, 950 Campbell Ave. (Room 7-127, G7E), West Haven, CT 06516-2770. E-mail: joyce.cramer@yale.edu. Received for publication 18 August 2003 and accepted in revised form 18 January 2004. J.C. is a member of an advisory panel of Novo Nordisk and has received honoraria or consulting fees from Novo Nordisk. Abbreviations: MEMS, Medication Event Monitor Systems; MUSE-P, Medication Usage Skills for Effec- tiveness Program; OHA, oral hypoglycemic agent. © 2004 by the American Diabetes Association. Reviews/Commentaries/Position Statements R E V I E W A R T I C L E 1218 DIABETES CARE, VOLUME 27, NUMBER 5, MAY 2004