Duckworth W. NEJM 8 Jan 2009; 360(2): 129-39. Supplement
Randomization: 20,027 patients screened, 17,788 (88.8%) excluded by chart review, 2239 (11.2%) provided consent, 448 (20.0%) excluded, 1791 (80%) underwent randomization. 899 received standard treatment, 892 received intensive treatment.
Baseline: Mean age 60.4y, diabbetes diagnosed for a mean of 11.5y, mean BMI 31.3, mean HBA1c was 9.4%, HTN in 72%, at least one cardiovascular event in 40%, 52% receiving insulin, 62% had microvascular complications.
Follow-up: SBP 125 vs 127, DBP 69 vs 68, LDL 80 vs 80, HDL 41 vs 40, quit smoking 77% vs 86%.
Primary Outcome:
HBA1c: 6.9% vs 8.4%
Time to first occurence of a cardiovascular event: no significant difference
MI: ARR 1.5%, NNT 66, p = 0.24
Stroke: ARR 0.8%, NNT 115, p = 0.32
Amputation: ARR 0.6%, NNT 152, p = 0.26
CV Death: ARR -1.0%, NNH 97, p = 0.26
Secondary Outcomes:
All Cause Mortality: ARR (-)0.8%, NNH 115, p = 0.62
Sudden Death: ARR (-)0.8%, NNH 115, p = 0.07
Otherwise, there were no significant differences between the groups
Microvascular Events: no significant differences
Adverse Events:
Hypoglycemia: Absolute Risk Increase 5.4%, NNH 18.5%, p = 0.000
METHODS
Sponsors: Sanofi-Aventis, GSK, Novo Nordisk, Roche, Kos Pharmaceuticals, Amylin
Study Type: open-label, randomized control trial
Time Frame: December 1, 2000 to May 30, 2003
Inclusion: Inadequate response to maximal doses of an oral agent or insulin therapy.
Exclusion: (a) Glycated hemoglobin < 7.5%, (b) CV event in last 6m, (c) advanced CHF, (d) severe angina, (e) life expectancy < 7y, (f) BMI > 40, (g) Cr > 1.6 mg/dL, ALT 3x nL
Treatment: Those with BMI > 27 started on metformin and rosiglitazone, if less than 27, started on glimepiride and rosiglitazone. Intensive group started on maximal doses and insulin added to keep HBA1c < 6%. Standard group received half maximal doses and insulin added to keep HBA1c < 9%.
Primary Outcome: time to first occurrence of composite of cardiovascular events (MI, stroke, death from CV causes, new or worsening CHF, surgical intervention for cardiac, cerebrovascular, or peripheral vascular disease, inoperable coronary artery disease, and amputation for ischemic gangrene)
Secondary Outcome: (1) New or worsening angina, (2) new TIA, (3) new intermittent claudication, (4) new critical limb ischemia, (5) and death from any cause. Also to include microvascular complications (retinopathy, nephropathy, neuropathy)
ADDITIONAL READING
ACCORD. Effects of intensive glucose lowering in type 2 diabetes. NEJM 2008; 358: 2545-59.
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