Baseline Characteristics of Participants in the Glycemia Reduction Approaches in Diabetes—A Comparative Effectiveness Study (GRADE)
Authors: WEXLER DEBORAH J. , KRAUSE-STEINRAUF HEIDI , KUHN ALEXANDER , CRANDALL JILL P. , FLOREZ HERMES , UNDERKOFLER CHANTAL , HOX SOPHIA H. , BACKMAN MICHAEL C. , ARODA VANITA ,   GRADE RESEARCH GROUP
Published: June 2018

GRADE is an NIDDK-sponsored, 36-center open-label randomized trial comparing the addition of one of the four most commonly used classes of glucose-lowering medications to metformin on long-term glycemic control and patient-centered outcomes in type 2 diabetes (T2D). Between June 2013 and June 2017, GRADE enrolled 5,047 patients age ≥ 30 years (y) (≥20 y in Native Americans [AI/AN]) at time of diagnosis, with T2D of &lt; 10 y, HbA1c 6.8-8.5%, and taking metformin (≥1,000 mg daily). Participants were randomly assigned to glimepiride, sitagliptin, liraglutide, or glargine. The primary metabolic outcome is time to HbA1c ≥7%. At baseline, participants were 57.0±10.0 y, 63.6% male, with racial/ethnic breakdown: 65.8% white, 19.8% African American, 18.4% Hispanic/Latino, 3.6% Asian, and 2.8% AI/AN. Mean HbA1c was 7.5±0.5% and BMI was 34.3±6.8 kg/m2. Sixty-nine percent were treated for hypertension; 6.6% had a history of heart attack or stroke. Participant characteristics were comparable across treatment arms. GRADE recruited a diverse cohort to inform decision-making regarding the long-term clinical effectiveness of four major classes of glucose-lowering medications added to metformin. Uniquely, GRADE includes patients with an intermediate duration of diabetes who require a second glucose-lowering medication. Primary results from GRADE are expected in 2021.Table 1: GRADE Study Cohort Baseline Demographics, Measurements, and Medical History as of November 29, 2017Overall N=5047Age at screening (yr) Mean ± SD57.0 ± 10.0Gender Male (%)3210 (63.6)Race by self-report American Indian / Alaska Native (%)142 (2.8) Asian (%)184 (3.6) Native Hawaiian or Other Pacific Islander (%)28 (0.6) Black or African-American (%)1001 (19.8) White (%)3320 (65.8) Other or more than one race (%)3(6.0)Ethnicity Hispanic/Latino (%)929 (18.4)Duration of diabetes (yr)4.0 ± 2.8Physical Measurements BMI (kg/m²)34.3 ± 6.8 Systolic BP (mmHg)128.3 ± 14.7 Diastolic BP (mmHg)77.3 ± 9.8Laboratory Tests HbA1c (%)7.5 ± 0.5 Cholesterol (mg/dL)163.8 ± 37.8 Triglycerides (mg/dL)154.0 ± 121.6 High Density Lipoprotein (HDL) (mg/dL)43.3 ± 12.1 Low Density Lipoprotein (LDL) (mg/dL)90.7 ± 31.4 Urine ACR (mg/g) [ Median (IQR) ]6.5 (3.2, 17.4) Fasting glucose (mg/dL)151.49 ± 30.9 Fasting C-peptide (nml/L)1.34 ± 0.6Medical History History of hypertension (%)3360 (66.6) History of elevated blood lipids (%)3646 (72.2) History of heart attack / stroke (%)331 (6.6)Family History of Diabetes Any first degree relative with diabetes (%)3522 (69.8)Means ± SD or Median and Interquartile Range (IQR) presented for continuous data; N(%) for categorical data.

Disclosure
D.J. Wexler: None. H. Krause-Steinrauf: None. A. Kuhn: None. J.P. Crandall: None. H. Florez: Advisory Panel; Self; Sanofi. C. Underkofler: None. S.H. Hox: None. M.C. Backman: None. V. Aroda: Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., AstraZeneca, Calibra Medical, Eisai Inc., Sanofi. Consultant; Self; Sanofi. Research Support; Self; Theracos, Inc.. Employee; Spouse/Partner; Merck & Co., Inc.. Other Relationship; Self; American Diabetes Association. Consultant; Self; ADOCIA. G. Research Group: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute. Other Relationship; Self; Bristol-Myers Squibb Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis, Roche Diagnostics Corporation, Becton, Dickinson and Company, Centers for Disease Control and Prevention, National Diabetes Education Program.