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 aim | Glycemic durability of second diabetes medication after metformin | Diabetes outcomes of intensive vs. conventional control after initial diagnosis of T2DM | Glycemic durability of initial diabetes medication | Subsample 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 intervention | Medications 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 diet | Rosiglitazone, metformin, or glyburide | NA |
| Primary outcome | Time to primary failure, defined as HbA1c ≥7% (53 mmol/mol), confirmed | Any diabetes-related end point,* diabetes-related death, all-cause mortality | Time to monotherapy failure (FPG >180 mg/dL [10 mmol/L], confirmed) for rosiglitazone, compared with metformin or glyburide | NA |
| Years of study conduct | 2013–2021 (planned) | 1977–1997 | 2000–2006 | 2011–2014 |
| Follow-up (years) | 5.2 (planned) | 10.0 (median) | 4.0 (median) | NA |
| Baseline characteristics of randomized cohort | ||||
| Demographic | ||||
| N | 5,047 | 3,867 | 4,360 | 120 (representing population n = 2,000,987) |
| Age (years) | 57.2 ± 10.0 | 53.2 ± 8.6 | 57 ± 10 | 57.9 ± 12.0 |
| Sex (% male) | 63.6 | 61.0 | 57.7 | 55.9 |
| Race/ethnicity | ||||
| Caucasian | 65.7 | 81 | 88.4 | 62.1† |
| African Ancestry | 19.8 | 8 | 4.0 | 15.1† |
| Hispanic | 18.4 | — | 4.4 | 12.1 |
| Asian | 3.6 | 10 (Indian Asian) | 2.4 | 8.5† |
| AI | 2.7 (AI/AN) | — | — | — |
| Clinical | ||||
| Duration of diabetes (years) | 4.2 ± 2.8 | New-onset | 96% <2 years | 4.2 ± 2.5 |
| Weight (kg) | 100.0 ± 22.3 | 77.5 ± 15.5 | 91.7 ± 19.5 | 95.8 ± 27.2 |
| BMI (kg/m2) | 34.3 ± 6.8 | 27.5 ± 5.2 | 32.2 ± 6.4 | 33.2 ± 8.2 |
| Systolic BP (mmHg) | 128.3 ± 14.7 | 135 ± 20 | 133 ± 15.3 | 132.2 ± 18.2 |
| Diastolic BP (mmHg) | 77.3 ± 9.9 | 82 ± 10 | 79.7 ± 9.0 | 74.1 ± 11.4 |
| Current smoker | 13.8 | 31 | 15 | 14.2 |
| History of CVD | 6.5 | NA | NA | 7.2 |
| Education | ||||
| <High school | 7.2 | 16.8 | ||
| High school graduate | 20.6 | 24.9 | ||
| Some college | 29.0 | 30.8 | ||
| ≥College degree | 43.2 | 27.5 | ||
| Biochemical | ||||
| Glycemia | ||||
| Fasting plasma glucose | ||||
| mg/dL | 151.5 ± 30.9 | 144 (128, 175)**‡ | 151.7 ± 26.2 | 161.7 ± 35.0 |
| mmol/L | 8.41 ± 1.72 | 8.0 (7.1, 9.7)**‡ | 8.42 ± 1.45 | 9.0 ± 1.9 |
| HbA1c | ||||
| % | 7.5 ± 0.5 | 7.1 ± 1.51 | 7.4 ± 0.93 | 7.4 ± 0.6 |
| mmol/mol | 58 ± 5.3 | 54 ± 16.5 | 57 ± 10.2 | 57 ± 6.6 |
| Fasting insulin | ||||
| pmol/L | 129.4 ± 95.4 | 92 (52, 160)§ | 150.7 ± 111 | 122.17 ± 96.36 |
| mU/L | 21.57 ± 15.9 | 15 (8.7, 27)§ | 25.12 ± 18.5 | 20.362 ± 16.06 |
| Lipids | ||||
| Total cholesterol | ||||
| mmol/L | 4.236 ± 0.976 | 5.4 ± 1.1 | 5.276 (4.58, 5.98)‡ | 4.74 ± 1.51 |
| mg/dL | 163.8 ± 37.8 | 209 ± 43 | 203.7 (177, 231)‡ | 183.19 ± 58.46 |
| LDL cholesterol | ||||
| mmol/L | 2.3 ± 0.8 | 3.5 ± 1.0 | 3.1 (2.5, 3.73)‡ | NA |
| mg/dL | 90.5 ± 31.7 | 135 ± 39 | 120 (97, 144)‡ | |
| HDL cholesterol | ||||
| mmol/L | 1.12 ± 0.27 | 1.07 ± 0.24 | 1.21 (1.02, 1.42)‡ | 1.12 ± 0.2 |
| mg/dL | 43.4 ± 10.6 | 41.4 ± 9.3 | 46.9 (39.2, 55.0)‡ | 43.3 ± 10.9 |
| Triglycerides | ||||
| mmol/L | 1.740 ± 1.374 | 2.35 (0.84–6.55)§ | 1.823 (1.28, 2.58)‡ | 2.8 ± 5.9 |
| mg/dL | 154.0 ± 121.6 | 208 (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.