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Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet. 2021;399(10321):259-269doi: 10.1016/S0140-6736(21)01640-8.
Shi, Q., Wang, Y., Hao, Q., Vandvik, P. O., Guyatt, G., Li, J., Chen, Z., Xu, S., Shen, Y., Ge, L., Sun, F., Li, L., Yu, J., Nong, K., Zou, X., Zhu, S., Wang, C., Zhang, S., Qiao, Z., Jian, Z., Li, Y., Zhang, X., Chen, K., Qu, F., Wu, Y., He, Y., Tian, H., & Li, S. (2022). Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet (London, England), 399(10321), 259-269. https://doi.org/10.1016/S0140-6736(21)01640-8
Shi, Qingyang, et al. "Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials." Lancet (London, England) vol. 399,10321 (2022): 259-269. doi: https://doi.org/10.1016/S0140-6736(21)01640-8
Shi Q, Wang Y, Hao Q, Vandvik PO, Guyatt G, Li J, Chen Z, Xu S, Shen Y, Ge L, Sun F, Li L, Yu J, Nong K, Zou X, Zhu S, Wang C, Zhang S, Qiao Z, Jian Z, Li Y, Zhang X, Chen K, Qu F, Wu Y, He Y, Tian H, Li S. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet. 2022 Jan 15;399(10321):259-269. doi: 10.1016/S0140-6736(21)01640-8. Epub 2021 Dec 08. PMID: 34895470.
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Lancet. 2022 Jan 15;399(10321):259-269. doi: 10.1016/S0140-6736(21)01640-8. Epub 2021 Dec 08.

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

Lancet (London, England)

Qingyang Shi, Yang Wang, Qiukui Hao, Per Olav Vandvik, Gordon Guyatt, Jing Li, Zhe Chen, Shishi Xu, Yanjiao Shen, Long Ge, Feng Sun, Ling Li, Jiajie Yu, Kailei Nong, Xinyu Zou, Siyi Zhu, Cong Wang, Shengzhao Zhang, Zhi Qiao, Zhongyu Jian, Ya Li, Xinyi Zhang, Kerun Chen, Furong Qu, Yuan Wu, Yazhou He, Haoming Tian, Sheyu Li

Affiliations

  1. 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.
  2. 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.
  3. Department of Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway.
  4. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
  5. Evidence-Based Medicine Centre, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  6. Evidence-Based Social Science Research Centre, School of Public Health, Lanzhou University, Lanzhou, China.
  7. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
  8. Rehabilitation Medical Centre, Rehabilitation Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
  9. Evidence-Based Nursing Centre, West China Hospital, Sichuan University, Chengdu, China.
  10. Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China.
  11. West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
  12. Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China.
  13. Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  14. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  15. 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. Electronic address: [email protected].

PMID: 34895470 DOI: 10.1016/S0140-6736(21)01640-8

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.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Conflict of interest statement

Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests.

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