Shi Qingyang, Wang Yang, Hao Qiukui, Vandvik Per Olav, Guyatt Gordon, Li Jing, Chen Zhe, Xu Shishi, Shen Yanjiao, Ge Long, Sun Feng, Li Ling, Yu Jiajie, Nong Kailei, Zou Xinyu, Zhu Siyi, Wang Cong, Zhang Shengzhao, Qiao Zhi, Jian Zhongyu, Li Ya, Zhang Xinyi, Chen Kerun, Qu Furong, Wu Yuan, He Yazhou, Tian Haoming, Li Sheyu
Department of Endocrinology and Metabolism and Department of Guideline and Rapid Recommendation, Cochrane China Center, MAGIC China Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Lancet. 2022 Jan 15;399(10321):259-269. doi: 10.1016/S0140-6736(21)01640-8. Epub 2021 Dec 8.
Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.
This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678.
14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27).
In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective.
1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.
如果生活方式改变未能成功，药物治疗为超重和肥胖的成年人提供了一种减轻体重的选择。我们总结了减肥药物利弊的最新证据。
这项系统评价和网状Meta分析包括从创刊至2021年3月23日对PubMed、Embase和Cochrane图书馆（CENTRAL）进行检索，以查找针对超重和肥胖成年人的减肥药物随机对照试验。我们进行了频率学派随机效应网状Meta分析以总结证据，并应用推荐分级评估、制定和评价框架来评定证据的确定性、计算绝对效应、对干预措施进行分类并呈现研究结果。该研究已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42021245678。
我们的检索共识别出14605条引文，其中143项符合条件的试验纳入了49810名参与者。除左卡尼汀外，所有药物与单纯生活方式改变相比均能降低体重；所有后续数据均指与生活方式改变的比较。高至中度确定性证据表明，安非他酮-托吡酯在减轻体重方面最有效（体重减轻≥5%的比值比[OR]为8.02，95%置信区间[CI]为5.24至12.27；体重变化百分比的均值差[MD]为-7.97，95%CI为-9.28至-6.66），其次是胰高血糖素样肽-1（GLP-1）受体激动剂（OR为6.33，95%CI为5.00至8.00；MD为-5.76，95%CI为-6.30至-5.21）。纳曲酮-安非他酮（OR为2.69，95%CI为2.11至3.43）、安非他酮-托吡酯（2.40，1.69至3.42）、GLP-1受体激动剂（2.17，1.71至2.77）和奥利司他（1.72，1.44至2.05）与导致停药的不良事件增加相关。在一项事后分析中，GLP-1受体激动剂司美格鲁肽在体重减轻5%或更多的可能性（OR为9.82，95%CI为7.09至13.61）和体重变化百分比（MD为-11.41，95%CI为-12.54至-10.27）方面均显示出比其他药物更大的益处，且不良事件风险与其他药物相似。
在超重和肥胖的成年人中，安非他酮-托吡酯和GLP-1受体激动剂被证明是最有效的减肥药物；在GLP-1激动剂中，司美格鲁肽可能是最有效的。
四川大学华西医院卓越学科1·3·5项目。
