Trends in Medication Use Among US Adults With Diabetes Mellitus: Glycemic Control at the Expense of Controlling Cardiovascular Risk Factors FREE

Successful reduction of cardiovascular disease (CVD) risk among people with diabetes mellitus is increasingly reliant on combination pharmacotherapy targeting its major risk factors, especially hypertension and high cholesterol level.¹ The impact of tight hyperglycemia control on CVD and mortality risk is currently unclear, but its control is a major part of comprehensive diabetes care and is also increasingly attained through combination therapy.^2- 4 We sought to examine the competing treatment priorities for US adults with diabetes by analyzing the use of antidiabetes, antihypertensive, and statin medications over time from the population-based National Health and Nutrition Examination Survey (NHANES) between 1999 and 2006.

NHANES 1999-2000, 2001-2002, 2003-2004, and 2005-2006 are serial cross-sectional surveys including nationally representative samples of the noninstitutionalized civilian US population identified through a stratified, multistage probability sampling design.⁵ The present analysis was limited to adults 20 years and older, who reported a history of diabetes mellitus. Data were collected through questionnaires (demographics and medical history), a physical examination (blood pressure), and blood collection (lipid, glucose, and hemoglobin A_1c [HbA_1c] levels). Use of antidiabetes, antihypertensive, and statin medications was ascertained via a series of questions about prescription medicines taken during the previous month and medication container examination.

The American Diabetes Association guidelines for standard medical care were used to determine the eligibility of participants with diabetes for antidiabetes, antihypertensive, and statin medications.² Eligibility for each medication included the following: hyperglycemia (HbA_1c level ≥7% [to convert to proportion of total hemoglobin, multiply by 0.01] or antidiabetes medication use); hypertension (systolic blood pressure [SBP] ≥130 mm Hg or diastolic blood pressure [DBP] ≥80 mm Hg or antihypertensive use); high cholesterol level (total cholesterol level ≥200 mg/dL [to convert to millimoles per liter, multiply by 0.0259] or lipid level–lowering medication use); and known CVD (≥1 CVD risk factor [family history of CVD, hypertension, cigarette smoking, or albuminuria] for those 40 years and older or 2 or more CVD risk factors for those younger than 40 years).

Among individuals with diabetes, the mean levels of blood pressure, total cholesterol, and HbA_1c were calculated for 1999-2000, 2001-2002, 2003-2004, and 2005-2006, separately, as was the percentage of those with hypertension and high cholesterol level. The percentage of adults with diabetes taking each class of antidiabetes and antihypertensive medications and statins and none, 1, 2, or 3 of these medications was determined by study period. The statistical significance of trends over time was tested by including study period as an ordinal variable in regression models. Analyses were weighted to represent the US population and conducted using SUDAAN statistical software (version 9; Research Triangle Institute, Research Triangle Park, North Carolina) to account for the complex survey design of NHANES.

Over the 8-year study period there was a significant decline in HbA_1c, SBP, and total cholesterol levels among those with diabetes (Table). Hemoglobin A_1c and cholesterol control increased between 1999-2000 and 2005-2006, with more than half (58.4%) of US adults with diabetes achieving HbA_1c levels less than 7% by 2005-2006. A large increase in hypertension control occurred between 1999-2000 and 2003-2004, while the prevalence of control declined between 2003-2004 and 2005-2006.

From 1999-2000 through 2005-2006 there were 10%, 15%, and 95% increases in antidiabetes, antihypertensive, and statin medication use, respectively. Among US adults with diabetes in 2005-2006, there was nearly universal antidiabetes medication use, but only 78% and 51% antihypertensive and statin medication use, respectively. The use of sulfonylureas declined from 1999-2000 to 2005-2006, while the use of metformin and thiazolidinediones increased. The percentage of adults with diabetes taking only 1 class of antidiabetes medication significantly declined, while the percentage taking 3 or more classes more than doubled.

An increase in the total number of medication types (ie, antidiabetes, antihypertensive, and statin medications) used by adults with diabetes occurred between 1999-2000 and 2005-2006 (Figure). By 2005-2006, the proportion taking all 3 of these medications more than doubled, while the percentage taking none of these medications was approximately half that in 1999-2000.

Between 1999-2000 and 2005-2006, the use of antidiabetes medications increased, with 90% of US adults with diabetes taking antidiabetes medication in 2005-2006. The use of antidiabetes medications substantially exceeded the proportion of eligible adults with diabetes taking antihypertensives and statins. The higher use of antidiabetes medications may be why the proportion of those with diabetes achieving an HbA_1c level lower than 7% was 50% and 35% greater than those achieving hypertension and cholesterol control, respectively. The present data also substantiate reports of increasing use of combined antidiabetes medication therapy, a decline in older generation oral medications such as sulfonylureas, and the rising use of the metformin and thiazolidinedione classes.⁶

The higher rates of antidiabetes medications compared with antihypertensive and statin medications highlights the concerns that a disproportionate emphasis is placed on controlling hyperglycemia at the expense of the more evidence-based CVD risk reduction strategies of controlling hypertension and high cholesterol level.^7- 8 Although research on competing priorities is limited, our study extends this literature by documenting that patients with diabetes are more likely to receive antidiabetes medication, which have not been shown to reduce CVD risk, rather than antihypertensive medications or statins.^7,9 Whether this phenomena is due to physician or patient preference is not discernable from our data.

Prior to landmark studies such as Action to Control Cardiovascular Risk in Diabetes (ACCORD)³ and Action in Diabetes and Vascular Disease (ADVANCE),⁴ published in 2008, there was wide support for tight glucose control. The impact of these new data on clinical practice has yet to be determined. Studies such as Steno-2¹⁰ that highlight the mortality benefit of aggressive hypertension and cholesterol control, along with our data, should encourage a renewed emphasis of their control among patients with diabetes.

Between 1999-2000 and 2005-2006, improvements occurred in the control of hyperglycemia, hypertension, and high cholesterol level among US adults with diabetes. Also, there was increasingly aggressive medication use with substantially more combination therapy in antidiabetes medications and use of newer agents. The data from this study support the perception that control of hyperglycemia frequently takes precedence over control of hypertension and high cholesterol level among adults with diabetes. These observations support the argument for a reprioritization of diabetes treatment goals emphasizing hypertension and cholesterol control before tight glycemic control as part of an evidence-based global CVD risk reduction effort.

Correspondence: Dr Mann, Division of General Internal Medicine, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, PO Box 1087, New York, NY 10029 (devin.mann@mssm.edu).

Author Contributions: Drs Mann and Muntner and Ms Ye had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Mann, Woodward, and Muntner. Acquisition of data: Mann and Muntner. Analysis and interpretation of data: Mann, Woodward, Ye, Krousel-Wood, and Muntner. Drafting of the manuscript: Mann, Woodward, Ye, and Muntner. Critical revision of the manuscript for important intellectual content: Mann and Krousel-Wood. Statistical analysis: Mann, Woodward, Ye, and Muntner. Administrative, technical, and material support: Mann and Muntner. Study supervision: Woodward.

Financial Disclosure: None reported.