Pharmacological interventions for addressing pediatric and adolescent obesity: A systematic review and network meta-analysis

Shuo Yang; Shuangqing Xin; Ronghui Ju; Peizhuo Zang

doi:10.1371/journal.pone.0314787

Peer Review History

Original SubmissionSeptember 12, 2024
12 Sep 2024 Author Response https://doi.org/10.1371/journal.pone.0314787.r001
7 Oct 2024 Decision Letter - Aleksandra Klisic, Editor PONE-D-24-40184Pharmacological Interventions for Addressing Pediatric and Adolescent Obesity: A Systematic Review and Network Meta-analysisPLOS ONE Dear Dr. Yang, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Nov 21 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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If any of the included studies are unpublished, include a link (URL) to the primary source or detailed information about how the content can be accessed. A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis. The table must include the following information for each study: Name of data extractors and date of data extraction Confirmation that the study was eligible to be included in the review. All data extracted from each study for the reported systematic review and/or meta-analysis that would be needed to replicate your analyses. If data or supporting information were obtained from another source (e.g. correspondence with the author of the original research article), please provide the source of data and dates on which the data/information were obtained by your research group. If applicable for your analysis, a table showing the completed risk of bias and quality/certainty assessments for each study or outcome. Please ensure this is provided for each domain or parameter assessed. For example, if you used the Cochrane risk-of-bias tool for randomized trials, provide answers to each of the signalling questions for each study. If you used GRADE to assess certainty of evidence, provide judgements about each of the quality of evidence factor. This should be provided for each outcome. An explanation of how missing data were handled. This information can be included in the main text, supplementary information, or relevant data repository. Please note that providing these underlying data is a requirement for publication in this journal, and if these data are not provided your manuscript might be rejected. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Yang et al. have performed a systematic review and network meta-analysis of pharmacologic interventions for pediatric and adolescent obesity. These are my comments: - The abstract section is so long in its current format. It should be reduced to a maximum of 250-300 words. - Authors should add strengths to their manuscript before the limitation. - A paragraph highlighting the future research perspective and possible gaps in the literature should be added before the conclusion section. - The references prior to 2010 could be updated with those after 2010 since they provide more up-to-date findings. Reviewer #2: The manuscript titled "Pharmacological Interventions for Addressing Pediatric and Adolescent Obesity: A Systematic Review and Network Meta-analysis" evaluated the effects of medications on obesity in pediatric and adolescent. The manuscript is well-written with fair methodology. I have some comments for improvement: 1- Define abbreviations in their first use and make sure that abbreviated forms are being used after the definition. 2- I found some typos and grammatical errors. A native review is required. 3- Add the strengths of your study before the limitations paragraph. 4- The tables will be published without colors, Update them in the revised version. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . 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Revision 1
30 Oct 2024 Author Response Dear Editors and Reviewers: Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “Pharmacological Interventions for Addressing Pediatric and Adolescent Obesity: A Systematic Review and Network Meta-analysis.” (ID: PONE-D-24-40184). Those comments are all valuable and very helpful for revising and improving our paper, as well as providing important guiding significance for our research. We have studied the comments carefully and have made corrections, which we hope will be met with approval. The revised portions are marked in red on the paper. The main corrections in the paper and the response to the reviewer’s comments are as follows: Responds to the editor's comments: In accordance with the requirements of the journal's data availability policy, we integrated the features of excluded references and the risk of bias assessment for each included study into the supplementary information of the article. For detailed information, please refer to Appendix 4 Supplemental Table 4 and Appendix 6 Supplemental Table 6. A special thanks to you for your good comments. Responds to the reviewer’s comments: Reviewer #1: We are very grateful for your professional comments on the methodology of this revised manuscript. According to your advice, we amended the relevant part of the manuscript. All of your questions were answered one-by-one. 1.Response to comment: (The abstract section is so long in its current format. It should be reduced to a maximum of 250-300 words.） Response: Thanks for the constructive suggestions to improve our manuscript. We have made the following changes to the abstract: Background Obesity significantly impacts the health outcomes of children and adolescents, necessitating a comprehensive study to evaluate the effects of various anti-obesity medications (AOMs) on weight-related and metabolic outcomes. Methods PubMed, EMBASE, and CENTRAL were searched for studies published up to January 3, 2024. We performed a network meta-analysis on randomized clinical trials that compared various treatments for pediatric and adolescent obesity, such as phentermine/topiramate, semaglutide, exenatide, liraglutide, topiramate, metformin, fluoxetine, metformin/fluoxetine, sibutramine, and orlistat. The study evaluated body mass index (BMI), BMI percentage change, weight, BMI-SDS, waist circumference, metabolic, anthropometric, and safety outcomes. Results The study gathered 2733 studies, including 30 articles that involved 3822 participants. The results of our research showed that PHEN/TPM was better at lowering BMI than exenatide, liraglutide, metformin, fluoxetine, Met/Flu, topiramate, orlistat, and sibutramine, with mean differences (MD) ranging from -10.29 to -1.28. Additionally, semaglutide demonstrated superior efficacy over other AOMs (MD ranged from -8.28 to -1.24). Various levels of certainty, ranging from very low to moderate, supported the findings. Furthermore, semaglutide demonstrated superior efficacy over exenatide (MD-12.43, 95% CI -23.95 to -0.30) regarding percentage change in BMI. Semaglutide also showed enhanced weight reduction effectiveness compared to seven other AOMs except for PHEN/TPM (MD ranging from -15.56 to -12.65). Similarly, PHEN/TPM displayed greater weight reduction effectiveness than seven other AOMs, except for semaglutide (MD ranged from -12.17 to -9.27). Moreover, semaglutide proved more effective in decreasing waist circumference when compared with other AOMs apart from PHEN/TPM (MD ranged from -11.61 to -6.07). Similarly, we found that PHEN/TPM, excluding semaglutide and sibutramine, was more effective in reducing waist circumference (MD ranged from -8.64 to -5.51). Conclusions The study found that semaglutide outperformed other AOMs in reducing BMI and additional weight-related outcomes in children and adolescents with obesity, while PHEN/TPM showed comparable efficacy. 2.Authors should add strengths to their manuscript before the limitation. Response: We have enhanced the manuscript with the following strengths: This study is the first comprehensive systematic review and network meta-analysis assessing all pharmacological classes for pediatric and adolescent populations with obesity, offering a synthesis of available therapeutic options, including weight reduction strategies and enhancements in cardiometabolic risk factors. However, our study has some limitations, which are worth further discussion. 3.A paragraph highlighting the future research perspective and possible gaps in the literature should be added before the conclusion section. Response: What we have added is as follows： Future of AOM for the pediatric population and research gaps The third generation of nutrient-stimulated hormone-based (NuSH) anti-obesity medications (AOM), which includes co- and tri-agonists that combine peptides such as GLP-1, glucose-dependent insulinotropic polypeptide (GIP), amylin, and glucagon, is poised to commence clinical trials in adolescents. The inaugural trial involving tirzepatide is anticipated to initiate in mid-2024. Subsequent studies should address limitations including long-term safety, durability of treatment response, and the inclusion of broader populations. The distinctive biopsychosocial context experienced by children and adolescents during cognitive, psychological, and pubertal development is essential for ensuring long-term safety. Future research should evaluate the real-world adoption of weight-loss pharmacotherapies among adolescents, their effects on metabolic health, and potential strategies to mitigate weight regain upon discontinuation. Clinicians are pivotal in educating patients regarding lifestyle modifications, pharmacotherapy options, and surgical interventions aimed at preventing adult obesity. Furthermore, future investigations should expand eligibility criteria to more accurately represent the demographics utilizing AOM. 4.The references prior to 2010 could be updated with those after 2010 since they provide more up-to-date findings. Response: We have updated the references prior to 2010 as follows： Reference 5. Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9(5):474-88. updated to: Chamay Weber C, Gal-Duding C, Maggio AB. Family based behavioral treatment in adolescents suffering from obesity: evolution through adulthood. BMC Pediatr. 2024;24(1):33. However, references 15, 16, 17, 24 and 26 were the original research references for this meta-analysis and we did not replace them. Special thanks to you for your good comments. Reviewer #2: 1.Define abbreviations in their first use and make sure that abbreviated forms are being used after the definition. Response: We have revised the use of abbreviations in accordance with your suggestion. 2.A review of typos and grammar is proposed. Response: We have checked the article for typos and grammar according to your request. 3.Add the strengths of your study before the limitations paragraph. Response: We have enhanced the manuscript with the following strengths: This study is the first comprehensive systematic review and network meta-analysis assessing all pharmacological classes for pediatric and adolescent populations with obesity, offering a synthesis of available therapeutic options, including weight reduction strategies and enhancements in cardiometabolic risk factors. 4.The tables will be published without colors, Update them in the revised version. Response: We have changed the color of the table. We tried our best to improve the manuscript and made some changes to it. These changes will not influence the content and framework of the paper. We appreciate the editors’ and reviewers' hard work earnestly and hope that the correction will be met with approval. Once again, thank you very much for your comments and suggestions. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0314787.r003
18 Nov 2024 Decision Letter - Aleksandra Klisic, Editor Pharmacological Interventions for Addressing Pediatric and Adolescent Obesity: A Systematic Review and Network Meta-analysis PONE-D-24-40184R1 Dear Dr. Yang, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Aleksandra Klisic Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0314787.r004
Formally Accepted
Acceptance Letter - Aleksandra Klisic, Editor PONE-D-24-40184R1 PLOS ONE Dear Dr. Yang, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Aleksandra Klisic Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0314787.r005

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