A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Effic Tolerability of Combination Therapy with Rosiglitazo Sulfonylurea in African American and Hispanic Ameri Patients with Type 2 Diabetes Inadequately Controlle Sulfonylurea Monotherapy Jaime A. Davidson, MD1; Stephen O. M c M o r n , PhD2; Brian R. W a t e r h o u s e , MS2; and Alexander R. Cobitz, MD 2 1Department of Medicine, University of Texas, Southwestern Medical School, Dallas, Texas; and 2CardioMetabolic Medicines Development Centre, GlaxoSmithKline, King of Prussia, Penn ABSTRACT Background: Type 2 diabetes mellitus is twice as prevalent in African Americans and Hispanic Ameri- cans as in non-Hispanic whites. However, the effec- tiveness and safety profile of rosiglitazone maleate used as combination therapy with sulfonylureas in the management of diabetes and its effect on cardiovascu- lar disease (CVD) biomarkers/parameters have not been studied in these populations. Objective: The purpose of this study was to deter- mine the efficacy and tolerability of the addition of rosiglitazone to a regimen of glyburide once daily in African American and Hispanic American patients with type 2 diabetes previously inadequately controlled with sulfonylurea monotherapy. Methods: This randomized, double-blind, placebo- controlled, parallel-group study was conducted at 38 centers in the United States. Eligible patients were aged _>21 years, had type 2 diabetes, a fasting plas- ma glucose (FPG) level _>140 mg/dL, and a glycosylat- ed hemoglobin (HbAxc) value ->7.5%, and had been treated with sulfonylurea monotherapy for at least 2 monthsbefore screening. Patients were assigned to receive treatment with glyburide 10 or 20 mg/d plus rosiglitazone 8 mg (GLY÷RSG) or placebo (GLY÷PBO) PO (tablets) QD for 24 weeks. The pri- mary efficacy end point was the change from base- line in HbAlc after 24 weeks of treatment. Secondary end points included change in FPG; proportion of pa- tients achieving HbAlc targets (<7.0% and <6.5%); and changes in biomarkers for CVD risk, including C-reactive protein (CRP), plasminogen activator in- hibitor (PAI)-I activity, fibrinogen, tissue plasminogen activator (tPA) antigen, von Willebrand factor (vWF), soluble vascular cell adhesion molecule (sVCAM), lipoprotein-associated phospholipase A 2 activity, and urinary albumin/creatinine ratio (UACR). Tolerability was assessed using physical examination, including vital-sign measurement, clinical laboratory tests, an adverse event (AE) reports collected at each study visit. Results: A total of 245 patients (101 African Ameri- can and 144 Hispanic American) were enrolled. Demo- graphic characteristics were comparable between the GLY÷RSG and GLY÷PBO groups: mean (SD) age (52 [11.9] vs 53 [10.4] years), HbAlc (9.2% [1.3%] vs 9.4% [1.4%]), sex (men/women, 45.3%/54.7% vs 48.3%/51.7%), race (African American/Hispanic American, 43.6%/56.4% vs 37.9%/62.1%), and mean (SD) weight (86.3 [18.8] vs 88.3 [19.4] kg). In the overall study population, treatment with GLY+RSG was associated with a significantly greater mean (95% CI) reduction from baseline in HbAlc compared with GLY+PBO (between-group A,-1.4% [-1.7% to-1.1%]; P < 0.001). When assessed by ethnicity, HbAlc values Data from this study were presented in abstract form at the American Diabetes Association Scientific Sessions, June 4, 2004, Orlando, Florida, and the WONCA World Conference, October 13, 2004, Orlando, Florida. Accepted for publication June 7, 2007. doi: 10.1016/j.clinthera.2007.09.011 0149-2918/$32.00 Printed in the USA. Reproduction in whole or part is not permitted. Copyright © 2007 Excerpta Medica, Inc.