成人超重和肥胖的药物治疗随机对照试验的系统评价和网络荟萃分析

 Abstract

Background

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.

Methods

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.

Findings

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).

Interpretation

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.

Funding

1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

摘要翻译（仅供参考）

背景介绍

药物治疗为超重和肥胖的成年人提供了一种选择，以便在生活方式调整失败的情况下减轻他们的体重。我们总结了有关降体重药物的好处和坏处的最新证据。

研究方法

这一系统回顾和网络荟萃分析包括从开始到2021年3月23日在PubMed、Embase和Cochrane图书馆（CENTRAL）中搜索关于成人超重和肥胖症患者降体重药物的随机对照试验。我们进行了频繁主义随机效应网络荟萃分析来总结证据，并应用建议分级评估、发展和评价框架来评定证据的确定性，计算绝对效果，对干预措施进行分类，并展示结果。该研究已在PROSPERO注册，CRD 42021245678。

研究结果

我们的搜索发现了14605条引文，其中143项符合条件的试验招募了49810名参与者。除左旋肉碱外，所有药物与单独的生活方式调整相比都降低了体重；随后的所有数字都指与生活方式调整的比较。高度到中度确定的证据表明，芬特明-托吡酯对降低体重最有效（体重减少≥5%的几率[OR]为8-02，95%CI为5-24至12-27；体重变化百分比的平均差异[MD]为-7-97，95%CI为-9-28至-6-66），其次是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-布洛芬（OR 2-69，95% CI 2-11至3-43）、芬特明-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）都与导致停药的不良事件增加有关。在一项事后分析中，semaglutide，一种GLP-1受体激动剂，在体重减轻5%或更多的可能性（OR 9-82，95% CI 7-09至13-61）和体重变化百分比（MD -11-41，95% CI -12-54至-10-27）方面，显示出比其他药物大得多的益处，而不良事件风险与其他药物相似。

解读

在超重和肥胖的成年人中，芬特明-托吡酯和GLP-1受体激动剂被证明是减少体重的最佳药物；在GLP-1激动剂中，塞马鲁肽可能是最有效的。

资助

1.3.5 四川大学华西医院优秀学科项目。