Dear Dr. Chiu,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Chuang etal conduct a retrospective study to investigate the efficacy of two different doses, multi-gastric

sites botulinum toxin A injections for weight control in patients with obesity. I listed my concerns as follows

Major Concerns

1. Diagnosis of the pricipants. In the manuscript, authors stated that pariticpants with BMI at least 25kg/M2 otherwise with complications were allowed to be enrolled. But please make it clear, whether these participants could be diagnosed with obesity or overweight or not.

2. Study design. Please clarify whether these pariticpants had maintained stable life style or weight (change less than 5%) for at least three months or even longer at baseline or not. Also, please also clarify whether the change of concomitant medicine or lifestyle change is allowed throughout the study.

3. Safety data was missed. Authors just simply described the efficacy data while didn't touch any adverse event like GI side effect which I believe is very important to evalute the treatment regimen together with efficacy data.

Minor

Overspeculation.

In the conclusion part, the authors claimed that this is a strong evidence, which is obviously inappropriate since it is not a RCT. Please correct.

Reviewer #2: This interesting study evaluated the outcome of intragastric BTX-A injections in 4 groups of patients receiving endoscopic injections at varying doses (300 IU or 400 IU) and sites (fundus and body or antrum and body). The results showed significant reductions in body weight, BMI, and body fat with gastric fundus and body injections. The authors concluded that endoscopic intragastric BTX-A injections effectively reduce body weight, BMI, and body fat, particularly with injections in the fundus and body regions.

The study was well conducted, and the article is well constructed. I have a few comments for the authors:

-It is mentioned that patients were required to follow a 1200 kcal liquid diet for 12 weeks, which is quite a long time. Did patients have any difficulties with the liquid diet? Did all patients keep their diet? Was there a recommended diet for patients after 12 weeks? Did you follow up with patients after changing the liquid diet? A liquid diet alone can result in significant weight loss and changing the diet after 12 weeks may lead to weight gain. A longer follow-up of patients after switching to a regular diet would be better.

-Were there any short-term or long-term complications after the procedure?

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Dear Dr. Chiu,

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 Oct 09 2025 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.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Eshetie Melese Birru, PhD

Academic Editor

PLOS ONE

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

**********

Reviewer #2: Dear authors,

Thank you for your response and for addressing the comments. I believe it would be beneficial to discuss the combined effect of a reductive diet and toxins in the discussion section, as well as the importance of long-term lifestyle choices in maintaining weight.

Additionally, if you have any considerations about the diet after three months, I would suggest including them in the manuscript.

**********

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Reviewer #2: No

**********

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Dear Dr. Chiu,

publication criteria  and not, for example, on novelty or perceived impact.

For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

==============================

Please submit your revised manuscript by Dec 05 2025 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.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Eshetie Melese Birru, PhD

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Although the study explores different dose–site combinations of intragastric botulinum toxin A (BTX-A), it lacks a placebo or standard-of-care control group.

This omission makes it impossible to isolate the pharmacological effect of BTX-A from that of the structured 1200 kcal liquid diet and repeated dietary counselling—all of which independently induce weight loss.

Without a control arm:

The reported reductions in body weight, BMI, and body fat could reflect dietary restriction rather than toxin efficacy.

The mixed-model analysis comparing “site” and “dose” groups assumes BTX-A is effective, yet there is no baseline-to-placebo benchmark to confirm this.

Prior RCTs have yielded heterogeneous results, emphasizing the need for clear differentiation between toxin and behavioral effects.

Required correction/comment:

The authors must explicitly acknowledge this as a major limitation and temper the conclusion that “endoscopic intragastric BTX-A injections effectively reduce body weight, BMI, and body fat.”

Alternatively, if historical or concurrent controls were available, these should be clearly described, with corresponding data or justification for comparability.

Future trials should include a randomized placebo-controlled design to validate the observed effect sizes.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

**********

Reviewer #2: (No Response)

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #2: No

**********

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Evaluating the Efficacy of Intragastric Botulinum Toxin A Injections with Two Different Quantities and Sites for Obesity

PONE-D-24-57405R3

Dear Dr. Cheng-Di,

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.

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Eshetie Melese Birru, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: