Johansson K, Neovius K, DeSantis S M, Rössner S, Neovius M
Department of Medicine, Obesity Unit, Karolinska Institute, Stockholm, Sweden.
Obes Rev. 2009 Sep;10(5):564-75. doi: 10.1111/j.1467-789X.2009.00581.x. Epub 2009 May 12.
The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo-controlled trials of 12-24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66-2.41) and orlistat (1.59; 1.21-2.08), but not sibutramine (0.98, 0.68-1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5-9%; NNH 14, 11-19), followed by orlistat (3%, 1-4%; NNH 39, 25-83), while no significant difference was seen for sibutramine (0.2%, -3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.
本文的目的是评估在奥利司他、西布曲明和利莫那班试验中因不良事件导致停药的风险。检索了1990年至2008年5月期间的Medline、EMBASE、Cochrane对照试验注册库以及已识别文章的参考文献列表。纳入了所有针对成年人、使用许可剂量、为期12 - 24个月的随机安慰剂对照试验。如果研究/研究组评估的是体重减轻后的体重维持情况，则将其排除。确定试验，使其符合纳入和排除标准并进行审查。提取关于参与者、干预措施和停药的数据，并根据既定标准对试验进行质量评级。采用随机效应模型来估计合并风险比、风险差异和伤害所需人数（NNH）。共有28项试验符合纳入标准（16项奥利司他试验、7项西布曲明试验和5项利莫那班试验）。因不良事件导致停药的风险比，利莫那班（2.00；1.66 - 2.41）和奥利司他（1.59；1.21 - 2.08）显著升高，但西布曲明未升高（0.98，0.68 - 1.41）。与安慰剂相比，利莫那班的风险差异最大（7%，5 - 9%；NNH 14，11 - 19），其次是奥利司他（3%，1 - 4%；NNH 39，25 - 83），而西布曲明无显著差异（0.2%， - 3至4%；NNH 500）。导致停药的最常见不良事件，奥利司他是胃肠道事件（40%），利莫那班是精神方面事件（47%）。西布曲明的相应信息未获取到。总之，现有的减肥药物在因不良事件导致停药的风险以及这些事件的潜在原因方面存在显著差异。鉴于有大量患者适合接受治疗，利莫那班较低的NNH令人担忧。
