Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials

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 132 eligible trials enrolled 48 209 participants. 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<middle dot>02, 95% CI 5<middle dot>24 to 12<middle dot>27; mean difference [MD] of percentage bodyweight change -7<middle dot>98, 95% CI -9<middle dot>27 to -6<middle dot>69) followed by GLP-1 receptor agonists (OR 6<middle dot>33, 95% CI 5<middle dot>00 to 8<middle dot>00; MD -5<middle dot>79, 95% CI -6<middle dot>34 to -5<middle dot>25). Naltrexone-bupropion (OR 2<middle dot>69, 95% CI 2<middle dot>10 to 3<middle dot>44), phentermine-topiramate (2<middle dot>40, 1<middle dot>68 to 3<middle dot>44), GLP-1 receptor agonists (2<middle dot>22, 1<middle dot>74 to 2<middle dot>84), and orlistat (1<middle dot>71, 1<middle dot>42 to 2<middle dot>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<middle dot>82, 95% CI 7<middle dot>09 to 13<middle dot>61) and percentage bodyweight change (MD -11<middle dot>40, 95% CI -12<middle dot>51 to -10<middle dot>29). 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. Copyright (c) 2024 Elsevier Ltd. All rights reserved.