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Response: We have renamed all files correctly

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Response: We have now uploaded PRISMA flowchart as Figure 1

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Response: We have written - All data are in the manuscript and/or supporting information files

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Response: Thank you for bringing this to our attention. We have carefully reviewed and revised Additional File 3 (now Table 1) to further protect participant confidentiality. Specifically, we have anonymized the participant-level data by replacing exact ages with age ranges, categorizing glycaemic control (rather than reporting exact blood glucose and HbA1c values), and removing specific laboratory results while retaining clinically relevant summaries. These revisions preserve the scientific content of the supplementary table while minimizing the risk of participant identification.

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Response: We have noted this

ADDITIONAL EDITOR COMMENTS

This study is of interest to the general readers as GLP1-RA is getting more and more important and widely prescribed. However, this manuscirpt should revise to faciliate reading and intepretation:

1. Please remove additional file 1 to the main text of methods.

Response: Thank you. This has been done

2. The additional file 2 should be figure 1

Response: Thank you. This has been done

3. The additional file 3 and 4 should be table 1 and 2 separately.

Response: Thank you. This has been done

4. The discussion is not sufficient, please refer to the related publications (PMID: 40175094; PMID: 39209334)

Response: Thank you. We have improved on the discussion.

REVIEWER'S RESPONSES TO QUESTIONS

Comments to the Author

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Reviewer #1: Yes

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

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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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: Given the rapidly expanding use of GLP-1 receptor agonists for diabetes and weight management. This systematic review summarizes reported cases of GLP-1RA-associated gastroparesis, focusing on clinical presentation, diagnostic evaluation, management, and outcomes. Overall, the review highlights the importance of recognizing persistent or severe gastrointestinal symptoms as a potential drug-related complication. However, several issues should be addressed.

1. The manuscript would benefit from a clearer distinction between GLP-1RA-induced gastroparesis and GLP-1RA-exacerbated pre-existing diabetic gastroparesis, particularly because several included cases had diabetes or prior symptoms suggestive of delayed gastric emptying.

Response: Thank you for this important observation. We agree that distinguishing de novo GLP-1RA-induced gastroparesis from exacerbation of pre-existing diabetic gastroparesis is clinically relevant. We have revised the Discussion to explicitly differentiate these entities by discussing cases that were more consistent with de novo drug-induced gastroparesis and those that more likely represented exacerbation or unmasking of pre-existing diabetic gastroparesis. Specifically, we note that several included cases had documented gastroparesis, previous gastroparesis episodes, or symptoms suggestive of delayed gastric emptying before GLP-1RA initiation, and are therefore more appropriately interpreted as exacerbations of underlying disease rather than de novo drug-induced gastroparesis.

2. Since six of the included reports were conference abstracts, the authors should discuss more explicitly how incomplete reporting may affect the reliability of patient characteristics, diagnostic details, management strategies, and outcomes.

Response: Thank you for this valuable suggestion. We have revised the Limitations section to explicitly discuss the implications of including conference abstracts. Specifically, we now note that conference abstracts frequently provide limited information on patient characteristics, diagnostic investigations, management strategies, follow-up, and clinical outcomes. We also explain that incomplete reporting may have limited our ability to compare cases, distinguish de novo GLP-1RA-induced gastroparesis from exacerbation of pre-existing gastroparesis, and comprehensively evaluate management approaches and outcomes. These additions to the limitations section, provide a clearer interpretation of how the inclusion of conference abstracts may have affected the reliability and completeness of the evidence synthesized in this review.

The statement that radiological investigations and endoscopy are sufficient to diagnose GLP-1RA-induced gastroparesis may be too strong. It would be more appropriate to state that these findings can support a suspected diagnosis after mechanical obstruction has been excluded.

Response: Thank you for this important observation. We agree that our original wording overstated the diagnostic role of radiological investigations and endoscopy. We have revised the Discussion to clarify that these investigations were primarily used to demonstrate gastric distension or retained gastric contents and to exclude mechanical obstruction. We now state that, when interpreted alongside the temporal relationship between symptom onset and GLP-1RA exposure, these findings supported a suspected diagnosis of GLP-1RA-associated gastroparesis rather than being sufficient to establish the diagnosis. We have also clarified that gastric emptying scintigraphy (GES) was performed mainly in patients with chronic or longstanding symptoms to confirm delayed gastric emptying and, in some cases, to document reversibility following withdrawal of the GLP-1RA. This revision more accurately reflects the findings of the included studies and avoids overstating the diagnostic role of radiological investigations and endoscopy.

The manuscript states that symptom onset ranged from hours to several months after GLP-1RA initiation; however, the temporal pattern is not clearly summarized. Please consider categorizing the included cases by time to onset to better characterize the clinical presentation.

Response: Thank you for this helpful suggestion. We have revised both the Results and Discussion sections to provide a clearer summary of the temporal pattern of symptom onset following GLP-1RA exposure. In the Results, we categorized the cases according to the interval between GLP-1RA exposure and symptom onset, distinguishing those that developed within one week from those that developed between one and three months after treatment initiation or dose escalation, while also describing cases in which the timing could not be precisely classified. In the Discussion, we expanded the interpretation of these findings by highlighting the variability in symptom onset and emphasizing that gastroparesis may occur not only shortly after treatment initiation but also following dose escalation, inappropriate re-initiation, unsupervised use, or switching between GLP-1RA agents. These revisions better characterize the temporal pattern of presentation and its clinical implications.

The Introduction or Discussion would benefit from a brief consideration of the clinical overlap between gastroparesis and functional dyspepsia, as symptoms such as nausea, vomiting, early satiety, bloating, and postprandial discomfort are not specific to gastroparesis (eg, PMID: 39944931 and PMID: 40973477).

Response: Thank you for this helpful suggestion. We agree that the symptoms of gastroparesis overlap substantially with those of functional dyspepsia and are therefore not specific to gastroparesis. We have revised the Clinical Presentation subsection of the Discussion to acknowledge this overlap. Specifically, we now note that symptoms such as nausea, vomiting, early satiety, postprandial fullness, epigastric pain, and bloating may also occur in functional dyspepsia, and emphasize that these symptoms should be interpreted within the overall clinical context, including their temporal relationship with GLP-1RA exposure, symptom severity and persistence, and the presence of features suggestive of delayed gastric emptying. We have also incorporated the recommended references to support this discussion.

The authors should consider adding a brief practical algorithm or summary pathway for clinicians, including symptom recognition, exclusion of obstruction, consideration of gastric emptying testing, GLP-1RA discontinuation, supportive treatment, and follow-up.

Response: Thank you for this valuable suggestion. We have addressed this comment by developing and incorporating a practical clinical algorithm (Figure 2) into the manuscript. The algorithm provides a concise, evidence-based summary of the recognition and management of suspected GLP-1RA-associated gastroparesis, including symptom recognition, assessment of the temporal relationship to GLP-1RA therapy, exclusion of alternative causes (including mechanical obstruction), diagnostic evaluation, GLP-1RA discontinuation, supportive treatment, and follow-up. We have also added a new subsection entitled "Practical clinical approach" in the Discussion to introduce the figure and highlight its intended use as a pragmatic clinical aid derived from the evidence synthesized in this systematic review, rather than as a formal clinical guideline.

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