Table 1.
Comparison of four trials of intensive glycemic control and CVD outcomes
| ACCORD | ADVANCE | VADT | UKPDS post-trial | |
|---|---|---|---|---|
| Clinical trials | NCT00000620 | NCT00145925 | NCT00032487 | ISRCTN75451837 |
| NIH listing | see website http://clinicaltrials.gov | see website http://clinicaltrials.gov | see website http://clinicaltrials.gov | see website http://controlled-trials.com |
| Design | RCT, AC, Phase III | RCT, PC, Phase III | RCT, AC, Phase III | RCT, AC, Phase III |
| Participant characteristics | ||||
| n | 10,251 | 11,140 | 1,791 | 3,277 |
| Mean age (years) | 62 | 66 | 60 | 63 |
| Duration of diabetes (years) | 10 | 8 | 11.5 | 17 |
| Sex (% male/female) | 39/61 | 42/58 | 97/3 | SI:60/40; M:46/54 |
| History of CVD (%) | 35 | 32 | 40 | None |
| BMI (kg/m2) | 32 | 28 | 31 | SI:29; M:32 |
| Mean baseline HbA1c (%) | 8.1 | 7.5 | 9.4 | SI:7.9; M:8,4 |
| On insulin at baseline (%) | 35 | 1.5 | 52 | 64 |
| Protocol characteristics | ||||
| HbA1c goals (%) (I vs S)a | <6.0 vs 7.0–7.9 | ≤6.5 vs ‘based on local guidelines’ | <6.0 (action if >6.5) vs planned separation of 1.5 | Aiming for fasting plasma glucose <6 mmol/L |
| Protocol for glycemic control (I vs S)a | Multiple drugs in both arms | Multiple drugs added to gliclizide vs multiple drugs with no gliclizide | Multiple drugs in both arms | Intensive therapy (either sulfonylurea or insulin/SI or, min overweight patients, metformin/M) vs corresponding conventional therapy group/C (dietary restriction) |
| Management of risk factors | Embedded BP and lipid trials | Embedded BP trial | Protocol for intensive treatment in both arms | None |
| On study characteristics | ||||
| Median duration of follow-up (years) | 3.5 (terminated early) | 5 | 5.6 | 8.8 |
| Achieved median HbA1c (%) (I vs S)a | 6.4 vs 7.5 | 6.4 vs 7.0 | 6.9 vs 8.5 | SI:7.9 vs 7.9; M:8.1 vs 8.1 |
| On insulin at study end (%) (I vs S)a | 77 vs 55a | 40 vs 24 | 89 vs 74 | Data not shown |
| On TZD at study end (%) (I vs S)a | 91 vs 58a | 17 vs 11 | 53 vs 42 | None |
| On statin at study end (%) (I vs S)a | 88 vs 88a | 46 vs 48 | 85 vs 83 | Data not shown |
| On aspirin at study end (%) (I vs S)a | 76 vs 76a | 57 vs 55 | 88 vs 86 | Data not shown |
| Smokers at study end (%) | 10 | 8 | 8 | Data not shown |
| Mean blood pressure at study end (mmHg) | ||||
| Intensive glycemic control arm | 126/67 | 136/74 | 127/68 | Data not shown |
| Standard glycemic control arm | 127/68 | 138/74 | 125/69 | Data not shown |
| Weight changes (kg) | ||||
| Intensive glycemic control arm | +3.5 | −0.1 | +7.8 | SI: +1.0 |
| Standard glycemic control arm | +0.4 | −1.0 | +3.4 | M: −1.0 |
| Severe hypoglycemia participants with 1 or more episodes during study (%) | ||||
| Intensive glycemic control arm | 16.2 | 2.7 | 21.2 | Data not shown |
| Standard glycemic control arm | 5.1 | 1.5 | 9.9 | Data not shown |
| Outcomes | ||||
| Definition of primary outcome | Nonfatal MI, nonfatal stroke, CVD death | Microvascular plus macrovascular (nonfatal MI, nonfatal stroke, CVD death) outcomes | Nonfatal MI, nonfatal stroke, CVD death, hospitalization for heart failure, revascularization | Any diabetes-related endpoint, diabetes-related death, death from any cause, MI, stroke, peripheral vascular disease, microvascular disease |
| HR for primary outcome (95% CI) | 0.90 (0.78–1.04) | 0.9 (0.82–0.98); macrovascular 0.94 (0.84–1.06) | 0.88 (0.74–1.05) | SI:0.91 (0.83–0.99); M:0.79 (0.66–0.95) |
| HR for mortality findings (95% CI) | 1.22 (1.01–1.46) | 0.93 (0.83–1.06) | 1.07 (0.81–1.42) | SI:0.87 (0.79–0.96); M:0.73 (0.59–0.89) |
*
Medication rates for ACCORD are for any use during the study.
Abbreviations: AC, active control; BMI, body mass index; BP, blood pressure; C, conventional therapy; CVD, cardiovascular disease; I, intensive glycemic control; M, metformin group; MI, myocardial infarction; PC, placebo control; RCT, randomized controlled trial; S, standard glycemic control; SI, sulfonylurea-insulin group; TZD, thiazolidinedione.