Arena Pharmaceuticals San Diego, California 92121, USA.
J Clin Endocrinol Metab. 2011 Oct;96(10):3067-77. doi: 10.1210/jc.2011-1256. Epub 2011 Jul 27.
Lorcaserin is a novel selective agonist of the serotonin 2C receptor.
Our objective was to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese and overweight patients.
This randomized, placebo-controlled, double-blind, parallel arm trial took place at 97 U.S. research centers.
Patients included 4008 patients, aged 18-65 yr, with a body mass index between 30 and 45 kg/m(2) or between 27 and 29.9 kg/m(2) with an obesity-related comorbid condition.
Patients were randomly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg once daily (QD), or placebo. All patients received diet and exercise counseling.
The ordered primary endpoints were proportion of patients achieving at least 5% reduction in body weight, mean change in body weight, and proportion of patients achieving at least 10% reduction in body weight at 1 yr. Serial echocardiograms monitored heart valve function.
Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5% of baseline body weight (47.2 and 40.2%, respectively) as compared with placebo (25.0%, P < 0.001 vs. lorcaserin BID). Least squares mean (95% confidence interval) weight loss with lorcaserin BID and QD was 5.8% (5.5-6.2%) and 4.7% (4.3-5.2%), respectively, compared with 2.8% (2.5-3.2%) with placebo (P < 0.001 vs. lorcaserin BID; least squares mean difference, 3.0%). Weight loss of at least 10% was achieved by 22.6 and 17.4% of patients receiving lorcaserin 10 mg BID and QD, respectively, and 9.7% of patients in the placebo group (P < 0.001 vs. lorcaserin BID). Headache, nausea, and dizziness were the most common lorcaserin-related adverse events. U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0% of patients on placebo and 2.0% on lorcaserin 10 mg BID.
Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo.
洛卡塞嗪是一种新型的 5-羟色胺 2C 受体选择性激动剂。
我们的目的是评估洛卡塞嗪对肥胖和超重患者体重、心血管危险因素和安全性的影响。
这是一项在美国 97 个研究中心进行的随机、安慰剂对照、双盲、平行分组试验。
纳入了 4008 名年龄在 18-65 岁之间、体重指数在 30-45kg/m(2)或 27-29.9kg/m(2)之间且伴有肥胖相关合并症的患者。
患者被随机分配以 2:1:2 的比例接受洛卡塞嗪 10mg 每日两次（BID）、洛卡塞嗪 10mg 每日一次（QD）或安慰剂治疗。所有患者均接受饮食和运动咨询。
序贯主要终点是体重至少减轻 5%的患者比例、体重平均变化和体重至少减轻 10%的患者比例，随访时间为 1 年。连续的超声心动图监测心脏瓣膜功能。
与安慰剂组（25.0%，P<0.001 与洛卡塞嗪 BID 相比）相比，接受洛卡塞嗪 10mg BID 和 QD 治疗的患者体重至少减轻 5%的比例显著更高（分别为 47.2%和 40.2%）。洛卡塞嗪 BID 和 QD 的体重减轻最小均方（95%置信区间）分别为 5.8%（5.5-6.2%）和 4.7%（4.3-5.2%），而安慰剂组为 2.8%（2.5-3.2%）（P<0.001 与洛卡塞嗪 BID 相比；最小均方差值为 3.0%）。接受洛卡塞嗪 10mg BID 和 QD 的患者体重减轻 10%的比例分别为 22.6%和 17.4%，安慰剂组为 9.7%（P<0.001 与洛卡塞嗪 BID 相比）。最常见的洛卡塞嗪相关不良事件是头痛、恶心和头晕。美国食品和药物管理局定义的心脏瓣膜病在安慰剂组和洛卡塞嗪 10mg BID 组中分别发生在 2.0%的患者中。
在生活方式改变方案的基础上联合使用洛卡塞嗪可使体重出现剂量依赖性减轻，与安慰剂相比，洛卡塞嗪减轻体重的效果显著更强。
