Department of Biostatistics, School of Public Health and Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Obesity (Silver Spring). 2012 Feb;20(2):330-42. doi: 10.1038/oby.2011.330. Epub 2011 Nov 3.
A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI ≥ 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment.
一项为期 56 周的随机对照试验评估了盐酸苯丁胺和托吡酯控释组合（PHEN/TPM CR）用于减肥（WL）和改善代谢的安全性和有效性。患有 II 类和 III 类肥胖症（BMI≥35kg/m2）的男性和女性被随机分配至安慰剂组、PHEN/TPM CR 3.75/23mg 组或 PHEN/TPM CR 15/92mg 组，同时接受低能量饮食。主要终点是体重减轻的百分比和达到 5%WL 的患者比例。次要终点包括腰围（WC）、收缩压和舒张压（BP）、空腹血糖和血脂测量。在主要分析中（至少有一次基线后体重测量值且至少服用一次分配药物或安慰剂的随机患者），安慰剂组、3.75/23mg 组和 15/92mg 组患者在 56 周时分别减轻了基线体重的 1.6%、5.1%和 10.9%（P<0.0001）。在分类分析中，安慰剂组有 17.3%、3.75/23mg 组有 44.9%和 15/92mg 组有 66.7%的患者在 56 周时体重减轻至少 5%的基线体重（P<0.0001）。与安慰剂相比，15/92mg 组患者的 WC、收缩压和舒张压、空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）变化显著更大。最常见的不良反应是感觉异常、口干、便秘、味觉障碍和失眠。安慰剂组、3.75/23mg 组和 15/92mg 组的退出率分别为 47.1%、39.0%和 33.6%。PHEN/TPM CR 对体重和代谢变量具有剂量依赖性影响，其方向预期是有益的，没有证据表明治疗引起严重不良事件。
