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AIMS: We evaluated differences in participants with type 2 diabetes (T2DM) enrolled in the GRADE study at VA vs non-VA sites, focusing on cardiovascular risk factors and rates of diabetes care target achievements. METHODS: We compared baseline characteristics between participants at VA (n=1216) and non-VA (n=3831) sites, stratifying analyses by cardiovascular disease (CVD) history. RESULTS: VA and non-VA participants had similar diabetes duration (4.0 years), HbA1c (7.5%), and BMI (34 kg/m(2)); however, VA participants had more individuals ≥65 years (37.3% vs 19.8%,p

OBJECTIVE GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort. RESEARCH DESIGN AND METHODS Participants were age ≥30 years at the time of diagnosis, with duration of T2DM RESULTS At baseline, GRADE’s 5,047 randomized participants were 57.2 ± 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/Latino. Duration of diabetes was 4.2 ± 2.8 years, with mean HbA1c of 7.5 ± 0.5% (58 ± 5.3 mmol/mol), BMI of 34.3 ± 6.8 kg/m2, and metformin dose of 1,944 ± 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA1c, 7.4% [57 mmol/mol]; BMI, 33.2 kg/m2; duration, 4.2 ± 2.5 years; and 7.2% with a history of cardiovascular disease). CONCLUSIONS The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin.

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 < 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.