Table 1.
Important trials of insulin therapy in ACS and non-ACS patients
| Trial and year published |
Population | Percent with diabetes |
Intervention | Total N | 1° clinical outcome |
Rate of outcome in intervention arm |
Rate of outcome in control arm |
p-value |
|---|---|---|---|---|---|---|---|---|
| ECLA-GIK pilot trial7 (1998) |
Acute MI with or without ST elevation |
16% | 3 arms: high-dose GIK, low-dose GIK and control (no GIK) |
407 | All–cause in-hospital mortality |
18 of 268 (6.7%) (both GIK arms combined) |
16 of 139 (11.5%) |
NS |
| GIPS8 (2003) |
Acute ST elevation MI |
11% | GIK infusion × 8–12 hours versus no GIK infusion |
940 | All-cause death at 30 days |
23 of 476 (4.8%) |
27 of 464 (5.8%) |
0.50 |
| GIPS-29–11 (2006) |
Acute ST elevation MI, Killip class I only |
10% | GIK infusion × 8–12 hours versus no GIK infusion |
889 | All-cause death at 30 days |
13 of 444 (2.9%) |
8 of 445 (1.8%) |
0.27 |
| CREATE-ECLA12,13 (2005) |
Acute ST elevation MI |
18% | GIK infusion × 24 hours versus no GIK infusion |
20,201 | All-cause death at 30 days |
1,004 of 10,088 (10.0%) |
976 of 10,107 (9.7%) |
0.45 |
| OASIS-6 GIK trial15 (2007) |
Acute ST elevation MI |
14% | GIK infusion × 24 hours versus no GIK infusion |
2,748 | All-cause death at 30 days |
104 of 1,374 (7.6%) |
92 of 1,374 (6.7%) |
0.36 |
| DIGAMI32,33 (1995) |
Acute MI with or without ST elevation |
100% | IV glucose-insulin (GI) × 24 hours followed by SC insulin × three months, versus no insulin |
620 | All-cause death at three month |
38 of 306 (12.4%) |
49 of 314 (15.6%) |
NS |
| DIGAMI-234 (2005) |
Acute MI with or without ST elevation |
100% | 3 arms: IV GI × 24 hours plus SC insulin × 3 mos; IV GI infusion × 24 hours only; or no insulin |
1,253 | All-cause death during follow-up (mean two years) |
111 of 474 (23.4%) and 107 of 473 (22.6%) |
59 of 306 (19.1%) |
0.157 |
| Hi-5 study35 (2006) |
Acute MI with or without ST elevation, admission glucos > 140 mg/dL |
48% e | Insulin drip for 24 hours to maintain glucose 72–180 mg/dL (4.0–9.9 mmol/L), versus standard care |
240 | All-cause in-hospital death |
4.8% | 3.5% | 0.75 |
| Leuven surgical ICU37 (2001) |
Surgical ICU on ventilator |
13% | Insulin infusion to maintain blood glucose 80–110 mg/dL (4.4–6.1 mmol/L) while in ICU, versus no insulin infusion |
1,548 | All-cause death in the ICU |
35 of 765 (4.6%) |
63 of 783 (8.0%) |
<0.04* |
| Leuven medical ICU41 (2006) |
Medical ICU | 17% | Insulin infusion to maintain blood glucose 80–110 mg/dL (4.4–6.1 mmol/L) while in ICU, versus no insulin infusion |
1,200 | All-cause death in-hospital |
222 of 595 (37.3%) |
242 of 605 (40.0%) |
0.33 |
| Glucontrol trial43 2007, (abstract only) |
Medical- surgical ICUs |
Not published |
Insulin infusion to achieve blood glucose 80–110 mg/dL (4.4–6.1 mmol/L), versus control 140–180 mg/dL (7.7–9.9 mmol/L) |
1,101 | All-cause death in the ICU |
16.7% | 15.2% | NS |
| VISEP study45 (2008) |
ICU patients with severe sepsis or septic shock |
30% | Insulin infusion to maintain blood glucose 80–110 mg/dL (4.4–6.1 mmol/L) while in ICU, versus control (treat only if glucose > 200 mg/dL [11.0 mmol/L]) |
537 | All-cause death at 28 days |
61 of 247 (24.7%) |
75 of 289 (26.0%) |
0.74 |
| NICE-SUGAR49–51 (ongoing) |
Medical ICU patients with Various conditions |
N/A | Intensive glucose control (81–108 mg/dL, 4.5–5.9 mmol/L) while in ICU, versus less intense glucose control (144–180 mg/dL, 7.9–9.9 mmol/L) |
Planned 6,100; over 5,600 already enrolled |
All-cause death at 90 days |
N/A | N/A | N/A |
| IMMEDIATE trial52–54 (ongoing) |
Acute MI with or without ST elevation and unstable angina |
N/A | GIK therapy initiated in the pre–hospital setting versus no GIK |
Planned 15,450 patients |
All-cause death at 30 days and one year |
N/A | N/A | N/A |
| SWEET-ACS trial55 (ongoing) |
Acute MI with or without ST elevation, admission glucose between 140–200 mg/dL (7.7–11.0 mmol/L) |
N/A | Intensified multifactorial risk factor control (including tight glucose control in-hospital) versus less intense risk factor control |
Planned 1,500 patients |
Composite of CV death, non-fatal MI, non-fatal stroke, heart failure at two years |
N/A | N/A | N/A |
| INTENSIVE trial54,57 (ongoing) |
Acute anterior ST elevation MI with admission glucose ≥ 140 mg/dL (7.7 mmol/L) |
N/A | Insulin-glucose infusion to maintain glucose at 90–130 mg/dL (4.9–7.2 mmol/L), versus standard care (treat only if glucose > 180 mg/dL, 9.9 mmol/L) |
Planned 700 patients |
Will document clinical end points, but primary end point is infarct size by cardiac MRI |
N/A | N/A | N/A |
| RECREATE pilot study58 (ongoing) |
Acute ST elevation MI with admission glucose > 144 mg/dL (8.0 mmol/L) |
NA | Insulin infusion to maintain plasma glucose in the range of 90–120 mg/dL (4.9–6.6 mmol/L), versus standard care |
Planned 500 patients |
Difference in glucose levels achieved at 24 hours, and seven and 30 days |
N/A | N/A | N/A |
*
p-value adjusted for multiple interim analyses of the primary outcome
Key: ACS = acute coronary syndrome; GI = glucose-insulin; GIK = glucose-insulin-potassium; ICU = intensive care unit; MI = myocardial infarction; N/A = not applicable; SC = subcutaneous; CV = cardiovascular; MRI = magnetic resonance imaging