Efficacy and safety of lorcaserin in obesity: a systematic review and meta-analysis of randomized controlled trials

<b>Background</b>: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin. <b>Research design and methods</b>: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs. <b>Results</b>: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ∆ −3.076 Kg; 95% CI, −3.49 to −2.66; P &lt; 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo. <b>Conclusions</b>: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache.

**背景**：氯卡色林（Lorcaserin）是一种新型选择性5-羟色胺2C受体激动剂，已获批用于肥胖症的治疗。多项Ⅲ期随机对照试验（randomized controlled trials, RCTs）已证实，氯卡色林可显著减轻受试者体重。
**研究设计与方法**：本研究系统检索了截至2019年7月31日的PubMed、Embase、Cochrane图书馆及ClinicalTrials.gov数据库，筛选出所有采用氯卡色林干预、随访时长≥1年且明确报告了与安慰剂对照的疗效及安全性结局的研究。随后，本研究分析了随机对照试验中氯卡色林对体重减轻、美国食品药品监督管理局（Food and Drug Administration, FDA）定义的瓣膜病、抑郁及自杀风险的影响。
**结果**：针对4项随机对照试验（总样本量N=16856）的荟萃分析显示，与安慰剂组相比，氯卡色林可显著降低受试者体重（均数差−3.076 kg；95%置信区间：−3.49~−2.66；P<0.00001）。与安慰剂组相比，氯卡色林在FDA定义的瓣膜病（相对风险RR=1.20；95%置信区间：0.89~1.63；P=0.24）、抑郁（RR=1.07；95%置信区间：0.80~1.43；P=0.67）及自杀风险（RR=1.43；95%置信区间：0.96~2.15；P=0.08）方面均未观察到显著差异。
**结论**：氯卡色林可轻度减轻体重，且未观察到明显的严重不良反应。该药物常见的不良反应包括恶心、头晕及一过性头痛。