Defronzo Ralph A, Banerji Maryann, Bray George A, Buchanan Thomas A, Clement Stephen, Henry Robert R, Kitabchi Abbas E, Mudaliar Sunder, Musi Nicolas, Ratner Robert, Reaven Peter D, Schwenke Dawn, Stentz Frankie B, Tripathy Devjit
Texas Diabetes Institute and University of Texas Health Science Center, San Antonio, TX, USA.
BMC Endocr Disord. 2009 Jul 29;9:17. doi: 10.1186/1472-6823-9-17.
Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.
METHODS/DESIGN: 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140-199 mg/dl). In addition, IGT subjects were required to have FPG = 95-125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2-3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated.Primary endpoint is conversion of IGT to T2DM based upon FPG >or= 126 or 2-hour PG >or= 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.
ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.
clinical trials.gov identifier: NCT00220961.
糖耐量受损（IGT）是一种糖尿病前期状态。如果能防止IGT进展为显性糖尿病，就可以避免与高血糖相关的并发症。本研究的目的是在一项前瞻性随机、双盲、安慰剂对照试验中，检验吡格列酮（艾可拓）是否能预防IGT进展为2型糖尿病（T2DM）。
方法/设计：通过口服葡萄糖耐量试验（OGTT）（2小时血浆葡萄糖 = 140 - 199 mg/dl）确定602名IGT受试者。此外，IGT受试者要求空腹血糖（FPG）= 95 - 125 mg/dl，且至少有一项其他高危特征。在随机分组前，所有受试者均测量了踝臂血压、收缩压/舒张压、糖化血红蛋白（HbA1C）、血脂谱，一部分受试者还进行了频繁采样静脉葡萄糖耐量试验（FSIVGTT）、双能X线吸收法（DEXA）以及颈动脉内膜中层厚度（IMT）的超声测定。在此之后，受试者被随机分为接受吡格列酮（45 mg/天）或安慰剂组，并每2 - 3个月返回进行FPG测定，每年进行OGTT。在18个月和研究结束时重复进行颈动脉IMT测量。招募工作持续24个月，受试者再随访24个月。在研究结束时（48个月）或糖尿病诊断时，重复进行OGTT、FSIVGTT、DEXA、颈动脉IMT及所有其他测量。主要终点是基于FPG≥126或2小时PG≥200 mg/dl将IGT转化为T2DM。次要终点包括吡格列酮是否能：（i）改善血糖控制；（ii）增强胰岛素敏感性；（iii）增强β细胞功能；（iv）改善心血管疾病危险因素；（v）使颈动脉IMT消退/延缓进展；（vi）使新诊断的糖尿病恢复为正常糖耐量。
“立即行动”研究旨在确定吡格列酮是否能预防/延缓高危IGT受试者进展为糖尿病，并确定吡格列酮对葡萄糖代谢发挥有益作用以预防/延缓T2DM发病的机制（改善胰岛素敏感性和/或增强β细胞功能）。
临床试验.gov标识符：NCT00220961。
