ADVANCE Trial Is intensive glucose control with …推进审判是强化血糖控制与u2026.pdfVIP

RxFiles.ca - Trial Summary L. Regier, B. Jensen - June 12, 2008 ADVANCE Trial 1,2,3: Is intensive glucose control with a gliclazide based regimen better than standard glucose control with a non-gliclazide based regimen in high risk, but not too hard to control T2DM? Trial Methodology  Who was in the trial? n=11,140; ~8yr hx of T2DM; age 66yr; 42%; mean A1C: 7.5%; FBG=8.5mmol/L; weight=78kg BMI=28 only 4% North American; 32% had hx of CV disease; all survived a 6wk pre-trial run-in period (13.5% withdrew after run-in) o Inclusion: age 55+ yrs; T2DM onset at age 30; a history of macrovascular or microvascular disease or 1+ additional risk factors o Exclusion: definite indication for, or contraindication to, any study treatments or a definite indication for long-term insulin at time of study entry (also, of 12,877 registered for a 6 week run in period; 13.5% withdrew 11,140 went on to study randomization)  A1C Target: Intensive group: 6.5%; Standard group: ~7% depending on local guidelines; randomized controlled; not blinded.  Intervention drugs: Gliclazide modified release 90%vs 2% {DIAMICRON MR 30 to 120mg 70.4% @ 120mg dose ($170/month)} + other drugs {other sulfonylureas 2% vs 57%; sequential addition of metformin 74% vs 67%, glitazones 17% vs 11%, acarbose 19% vs 13%, insulin 40% vs 24% basal +/- short acting insulin} o Intensive patients also had 31 study visits compared to 11 for standard group (3x more contact with health providers) o 2x2 factorial design (other arm of trial, perindopril + indapamide vs placebo previously published Patel, Lancet 2007 4)  Primary (1) Endpoints: Composites of major macrovascular (CV death, non-fatal MI/stroke) major microvascular events (new/worsening nephropathy