Obesity Clinical Trials Programme, Duke University Medical Center, Durham, NC 27710, USA.
Lancet. 2011 Apr 16;377(9774):1341-52. doi: 10.1016/S0140-6736(11)60205-5. Epub 2011 Apr 8.
Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors.
In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787.
Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events.
The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.
Vivus.
肥胖与预期寿命缩短以及心血管疾病、癌症和其他原因导致的死亡率增加有关。因此，我们评估了两种剂量的苯丁胺加托吡酯控释组合作为辅助饮食和生活方式改变的方法，用于减轻超重和肥胖患者的体重和降低代谢风险，这些患者有两种或多种合并症（高血压、血脂异常、糖尿病或糖尿病前期、或腹部肥胖）。
在这项 56 周的 3 期临床试验中，我们随机分配了超重或肥胖成年人（年龄 18-70 岁），体重指数为 27-45kg/m²，且有两种或更多种合并症（高血压、血脂异常、糖尿病或糖尿病前期、或腹部肥胖），接受安慰剂、每日一次的苯丁胺 7.5mg 加托吡酯 46.0mg 或每日一次的苯丁胺 15.0mg 加托吡酯 92.0mg，比例为 2:1:2，在 93 个美国中心进行。药物通过口服给药。患者通过使用计算机生成的算法随机分配，该算法通过交互式语音应答系统实施，并按性别和糖尿病状态分层。调查人员、患者和研究赞助商对治疗情况不知情。主要终点是体重变化的百分比和至少 5%体重减轻的患者比例。分析是按意向治疗进行的。这项研究在美国临床试验数据库注册，编号为 NCT00553787。
在 2487 名患者中，994 名被分配到安慰剂组，498 名被分配到苯丁胺 7.5mg 加托吡酯 46.0mg 组，995 名被分配到苯丁胺 15.0mg 加托吡酯 92.0mg 组；分别有 979、488 和 981 名患者被分析。56 周时，体重变化分别为-1.4kg（最小二乘均值-1.2%，95%CI-1.8 至-0.7）、-8.1kg（-7.8%，-8.5 至-7.1；p<0.0001）和-10.2kg（-9.8%，-10.4 至-9.3；p<0.0001），患者分别接受安慰剂、苯丁胺 7.5mg 加托吡酯 46.0mg 和苯丁胺 15.0mg 加托吡酯 92.0mg。204 名（21%）患者达到至少 5%的体重减轻，安慰剂组为 303 名（62%；比值比 6.3，95%CI 4.9 至 8.0；p<0.0001），苯丁胺 7.5mg 加托吡酯 46.0mg 组为 687 名（70%；9.0，7.3 至 11.1；p<0.0001），苯丁胺 15.0mg 加托吡酯 92.0mg 组为 687 名（70%；9.0，7.3 至 11.1；p<0.0001）；至少减轻 10%体重的患者人数分别为 72 名（7%）、182 名（37%；7.6，5.6 至 10.2；p<0.0001）和 467 名（48%；11.7，8.9 至 15.4；p<0.0001）。最常见的不良事件是口干（24 例[2%]、67 例[13%]和 207 例[21%]，分别在接受安慰剂、苯丁胺 7.5mg 加托吡酯 46.0mg 和苯丁胺 15.0mg 加托吡酯 92.0mg 的患者中）、感觉异常（20 例[2%]、68 例[14%]和 204 例[21%]）、便秘（59 例[6%]、75 例[15%]和 173 例[17%]）、失眠（47 例[5%]、29 例[6%]和 102 例[10%]）、头晕（31 例[3%]、36 例[7%]和 99 例[10%]）和味觉障碍（11 例[1%]、37 例[7%]和 103 例[10%]）。38 名（4%）接受安慰剂的患者、19 名（4%）接受苯丁胺 7.5mg 加托吡酯 46.0mg 的患者和 73 名（7%）接受苯丁胺 15.0mg 加托吡酯 92.0mg 的患者出现了与抑郁相关的不良事件；28 名（3%）、24 名（5%）和 77 名（8%）出现了与焦虑相关的不良事件。
苯丁胺和托吡酯联合，加上以办公室为基础的生活方式干预，可能是肥胖的一种有价值的治疗方法，可以由家庭医生提供。
Vivus。
