Table 2

Comparison of GRADE study to UKPDS, ADOPT, and GRADE-eligible NHANES cohort

GRADE (1)UKPDS (20)ADOPT (3,21)NHANES (16)
Primary study aimGlycemic durability of second diabetes medication after metforminDiabetes outcomes of intensive vs. conventional control after initial diagnosis of T2DMGlycemic durability of initial diabetes medicationSubsample of NHANES participants meeting similar criteria (below) as GRADE (n = 120 [unweighted])
Study characteristics
 Key eligibility criteria• Age ≥30 years• Age 25–65 years• Age 30–75 years• Age ≥30 years
• T2DM <10 years• Newly diagnosed with T2DM• T2DM ≤3 years• T2DM <10 years
• HbA1c 6.8–8.5% (51–69 mmol/mol) taking metformin monotherapy• Mean FPG 110–270 mg/dL (6.1–15.0 mmol/L) after 3 months’ diet treatment • FPG 126–180 mg/dL (7–10 mmol/L) with lifestyle management alone• HbA1c 6.8–8.5% (51–69 mmol/mol) taking metformin monotherapy
 Randomized interventionMedications representing four classes: Sulfonylurea (glimepiride), DPP-4 inhibitor (sitagliptin), GLP-1 analog (liraglutide), or insulin (glargine)Intensive glycemic control with sulfonylurea or insulin or metformin (aim FPG <108 mg/dL (6 mmol/L), or conventional control with dietRosiglitazone, metformin, or glyburideNA
 Primary outcomeTime to primary failure, defined as HbA1c ≥7% (53 mmol/mol), confirmedAny diabetes-related end point,* diabetes-related death, all-cause mortalityTime to monotherapy failure (FPG >180 mg/dL [10 mmol/L], confirmed) for rosiglitazone, compared with metformin or glyburideNA
 Years of study conduct2013–2021 (planned)1977–19972000–20062011–2014
 Follow-up (years)5.2 (planned)10.0 (median)4.0 (median)NA
Baseline characteristics of randomized cohort
 Demographic
  N5,0473,8674,360120 (representing population n = 2,000,987)
  Age (years)57.2 ± 10.053.2 ± 8.657 ± 1057.9 ± 12.0
  Sex (% male)63.661.057.755.9
  Race/ethnicity
   Caucasian65.78188.462.1
   African Ancestry19.884.015.1
   Hispanic18.44.412.1
   Asian3.610 (Indian Asian)2.48.5
   AI2.7 (AI/AN)
 Clinical
  Duration of diabetes (years)4.2 ± 2.8New-onset96% <2 years4.2 ± 2.5
  Weight (kg)100.0 ± 22.377.5 ± 15.591.7 ± 19.595.8 ± 27.2
  BMI (kg/m2)34.3 ± 6.827.5 ± 5.232.2 ± 6.433.2 ± 8.2
  Systolic BP (mmHg)128.3 ± 14.7135 ± 20133 ± 15.3132.2 ± 18.2
  Diastolic BP (mmHg)77.3 ± 9.982 ± 1079.7 ± 9.074.1 ± 11.4
  Current smoker13.8311514.2
  History of CVD6.5NANA7.2
  Education
   <High school7.216.8
   High school graduate20.624.9
   Some college29.030.8
   ≥College degree43.227.5
 Biochemical
  Glycemia
   Fasting plasma glucose
    mg/dL151.5 ± 30.9144 (128, 175)**151.7 ± 26.2161.7 ± 35.0
    mmol/L8.41 ± 1.728.0 (7.1, 9.7)**8.42 ± 1.459.0 ± 1.9
   HbA1c
    %7.5 ± 0.57.1 ± 1.517.4 ± 0.937.4 ± 0.6
    mmol/mol58 ± 5.354 ± 16.557 ± 10.257 ± 6.6
   Fasting insulin
    pmol/L129.4 ± 95.492 (52, 160)§150.7 ± 111122.17 ± 96.36
    mU/L21.57 ± 15.915 (8.7, 27)§25.12 ± 18.520.362 ± 16.06
  Lipids
   Total cholesterol
    mmol/L4.236 ± 0.9765.4 ± 1.15.276 (4.58, 5.98)4.74 ± 1.51
    mg/dL163.8 ± 37.8209 ± 43203.7 (177, 231)183.19 ± 58.46
   LDL cholesterol
    mmol/L2.3 ± 0.83.5 ± 1.03.1 (2.5, 3.73)NA
    mg/dL90.5 ± 31.7135 ± 39120 (97, 144)
   HDL cholesterol
    mmol/L1.12 ± 0.271.07 ± 0.241.21 (1.02, 1.42)1.12 ± 0.2
    mg/dL43.4 ± 10.641.4 ± 9.346.9 (39.2, 55.0)43.3 ± 10.9
   Triglycerides
    mmol/L1.740 ± 1.3742.35 (0.84–6.55)§1.823 (1.28, 2.58)2.8 ± 5.9
    mg/dL154.0 ± 121.6208 (74–580)§161.3 (113, 228)246.5 ± 518.7
  • Continuous data are reported as the mean ± SD or as indicated and categorical data as the percentage. FPG, fasting plasma glucose; NA, not available.

  • *Defined as sudden death, hyper- or hypoglycemia-related death, myocardial infarction, angina, heart failure, stroke, renal failure, amputation, vitreous hemorrhage, retinopathy requiring photocoagulation, and blindness.

  • **Fasting serum glucose reported (not plasma).

  • †Non-Hispanic.

  • ‡Median (interquartile range) reported.

  • §Geometric mean, 1 SD reported.