Polypharmacy With Oral Antidiabetic Agents: An Indicator of Poor Glycemic Control

Published Online: August 01, 2006
Cynthia J. Willey, PhD; Susan E. Andrade, ScD; Joseph Cohen, MD; Jackie C. Fuller, MPH; and Jerry H. Gurwitz, MD

Objective: To evaluate antidiabetic drug treatment patterns and glycemic control among patients diagnosed with type 2 diabetes mellitus.

Study Design: Retrospective study using the automated databases of a 200 000-member HMO.

Methods: The study population consisted of patients ≥18 years of age with documented type 2 diabetes mellitus from January 1, 2002, through December 31, 2002. We determined the proportion of patients who had optimal glycemic control (glycosylated hemoglobin <7%) during the 6 months after the initial documentation of diabetes during calendar year 2002 (index date).

Results: Of the 4282 patients who met the inclusion criteria, 1050 (25%) received 1 oral agent, 486 (11%) received 2 oral agents, 56 (1%) received ≥3 oral agents, 84 (2%) received insulin and an oral agent, and 107 (2%) received insulin exclusively within 90 days after the index date. Among the 1075 patients receiving antidiabetic drug therapy who had a laboratory test result documented, 414 (39%) had optimal glycemic control. Optimal control was most frequent among patients receiving 1 oral agent (47%) and least frequent among patients receiving ≥3 oral agents (13%) (P <.01). Patients with a prior history of suboptimal glycemic control were less likely to have optimal glycemic control.

Conclusions: Multiple oral antidiabetic agents may serve as a marker for more severe, uncontrolled diabetes. The vast majority of patients treated with multiple oral antidiabetic agents had suboptimal glycemic control, suggesting a need for intensified efforts to treat this particular group of patients to recommended goal levels.

(Am J Manag Care. 2006;12:435-440)

Diabetes mellitus is a major cause of morbidity and mortality worldwide. The number of Americans with diagnosed diabetes is projected to increase 165% from 11 million in 2000 to 29 million in 2050,1 resulting in a large number of patients requiring lifetime treatment with antidiabetic agents or insulin. Diabetes presents an enormous economic burden to the United States. Direct medical expenditures attributable to diabetes totaled approximately $92 billion in 2002; more than 25% of the expenditures were attributable to treating diabetes-related complications.2

Optimal glycemic control is critical for reducing the risk of diabetic complications. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study (UKPDS) provided evidence of the relationship between hyperglycemia and long-term diabetic complications.3,4 The UKPDS study provided strong evidence that intensive therapy significantly reduced the risk of microvascular complications in patients with type 2 diabetes. The American Diabetes Association recommends treating diabetic patients to a glycosylated hemoglobin (A1C) level of less than 7%.5 However, the majority of diabetes patients still do not achieve recommended target values.6,7 A preliminary report based on National Health and Nutrition Examination Survey (NHANES) data found that the rate of glycemic control (as defined by an A1C level of <7%) declined from 44.5% in NHANES III (1988-1994) to 35.8% in NHANES 1999-20006; however, the NHANES 1999-2000 data were based on a small number of diabetes patients (n = 372). Another study among patients included in the Kaiser Permanente Northern California Diabetes Registry similarly reported low rates of glycemic control, with 30% of the diabetic population having an A1C level of 7% or less from 1999 through 2000.7 Rates of healthcare access and utilization, screening for diabetes complications, and the rate of treatment of hyperglycemia are high; however, health status and outcomes are unsatisfactory. There are likely to be multiple reasons for this discordance, including intractability of diabetes to current therapies, patient self-care practices, and medical care practices.8

The newer medications introduced during the past decade provide additional options for treating patients with type 2 diabetes. The availability of many new options may have a large impact on current antidiabetic therapy patterns and the rates of glycemic control. We undertook the present study to document current treatment patterns and glycemic control among patients with type 2 diabetes in a large, population-based sample.


Study Population and Design

A retrospective study was conducted among patients enrolled in a mixed-model, not-for-profit HMO operating in New England. The study population included HMO members who were 18 years of age or older and who had a diagnosis code for type 2 diabetes mellitus (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 250.x0 or 250.x2) from January 1, 2002, through December 31, 2002, as documented in the HMO administrative databases. Additional eligibility criteria included continuous enrollment in the staff-model component with prescription drug coverage for the 365 days before and 180 days after the initial documentation of diabetes (index date) during calendar year 2002. Members with a diagnosis code for gestational diabetes (ICD-9-CM 648) or type 1 diabetes mellitus (ICD-9-CM 250.x1 or 250.x3) were excluded from the study. Information on patient sex and age, health plan enrollment status, prescription drug dispensings, inpatient and outpatient diagnoses and procedures, and laboratory test results was obtained from HMO automated databases for the period 365 days before and 180 days after the index date. The institution's human-subjects committee reviewed and approved the study.

Identification and Categorization of Antidiabetic Drug Use

For each patient, antidiabetic medications dispensed during the 90 days after the index date were identified, and therapy was classified according to the total number of unique agents dispensed, based on the agents' generic names. Therapy was categorized as "1 oral agent," "2 oral agents," "3 or more oral agents," "insulin plus an oral agent," "insulin use exclusively," or "no antidiabetic medications."

Assessment of Glycemic Control

The HMO automated databases were used to identify the patients' current and prior history of glycemic control. Current optimal glycemic control was determined using the most recent laboratory test result for A1C during the 6 months (180 days) after the index date and was defined as an A1C level of less than 7% during the 6 months after the index date. Similarly, prior history of glycemic control was determined by using the most recent laboratory test result for A1C during the year (365 days) before the index date.

Identification and Definition of Other Patient Characteristics

The HMO automated databases were used to identify the patients' age on the index date; sex; antidiabetic drug therapy during the 90 days before the index date (categorized as outlined above); diagnosis of coronary heart disease (ICD-9-CM 410 to 414.99), hypertension (ICD-9-CM 401.x), or hypercholesterolemia (ICD-9-CM 272.x or dispensing of a cholesterol-lowering drug) during the previous year; utilization of health services; medication adherence; and comorbidity score. The total numbers of ambulatory visits, diabetes-related ambulatory visits (office visits including ICD-9-CM code 250.x1 or 250.x3), and hospitalizations during the previous year were determined.

Medication adherence during the year before the index date was estimated based on the supply dispensed (in days) from the first dispensing date of an oral antidiabetic drug during the previous year to the index date, divided by the number of days between the first dispensing date and the index date (percent days on therapy). If 1 prescription was dispensed during the time interval of a previous prescription, the overlapping number of days, supply was not duplicated.

Comorbidity was assessed using the chronic disease score developed by Clark and colleagues for prediction of healthcare costs, which is based on age, sex, and number of dispensings of prescription drugs.9 The chronic disease score is a claims-based, risk-adjustment metric that uses drug-dispensing information as a marker for chronic illness. The scores have been found to be predictive of utilization of healthcare resources, with higher scores reflecting higher healthcare costs. The scores also have been found to be predictive of hospitalization.10

Statistical Analysis

Descriptive analyses were used to estimate the proportion of patients to whom each type of antidiabetic drug therapy was dispensed and the proportion who had specific characteristics. For patients receiving antidiabetic medications who had a laboratory test value documented in the 6 months after the index date, the percentage with optimal glycemic control was estimated overall and according to patient characteristics. Logistic regression was used to estimate the strength of the association between patient characteristics and optimal glycemic control, with models constructed including variables for patient age; sex; antidiabetic drug therapy; past history of glycemic control; diagnosis of coronary heart disease, hypertension, or hypercholesterolemia; prior hospitalization; diabetes-related office visits during the previous year; medication adherence; and chronic disease score. Analyses of glycemic control based on an A1C value of less than 8% also were performed, but are not presented; the associations between glycemic control and patient characteristics were similar to those results based on an A1C value of less than 7%.


A total of 4282 members who were diagnosed with type 2 diabetes mellitus met the inclusion criteria. The mean age of the study population was 64 years (range, 20-96 years) and 46% (n = 1951) were female. Characteristics of the study population are shown in Table 1. During the 90 days after the index date, 1050 patients (25%) received 1 oral agent, 486 (11%) received 2 oral agents, 56 (1%) received 3 or more oral agents, 84 (2%) received insulin and an oral agent, 107 (2%) received insulin exclusively, and 2499 (58%) received no antidiabetic medications. The most common medications dispensed to patients taking 2 oral agents were a sulfonylurea and metformin (428 patients), and the most common medications dispensed to patients taking 3 or more agents were a sulfonylurea, metformin, and a thiazolidinedione (52 patients).

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