The Comparative Safety and Efficacy of Resmetirom and Semaglutide in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I would like to thank the authors for producing such an interesting and important piece. In this work, the authors provide a valuable and timely comparison of resmetirom and semaglutide for MASLD, addressing a significant clinical question in an evolving therapeutic landscape. The manuscript is well-structured, adhering to PRISMA guidelines, and offers a clear narrative synthesis of the current evidence.

The authors have tackled a highly relevant topic, comparing two promising agents with different mechanisms of action for MASLD, a condition with a growing global health burden. In their discussion, they effectively synthesize the efficacy and safety profiles of both drugs, highlighting their respective.

However, some clarifications are necessary in order for the review to be accepted for publication.

1. While the introduction explains the shift from NAFLD to MASLD , the primary objective in the methods section refers to "NAFLD", and "NAFLD" is also used as a keyword. Consistently using MASLD/MASH throughout the manuscript, especially in objectives and keywords (perhaps with an initial explanatory note), would align with current nomenclature and strengthen the contemporary relevance.
2. Table 2, which compares resmetirom and semaglutide, currently has a general citation for the studies by Harrison (ref 14) and Newsome (ref 15). For enhanced clarity and direct traceability, the authors could consider referencing the specific primary trial publications for the quantitative data presented within the table.
3. The Comparative Insights subsection in the Results section is useful but relatively brief. This could be woven more thoroughly into the main results presentation for each drug. For instance, when discussing an outcome like fibrosis improvement for resmetirom, a direct comparative statement about semaglutide performance on the same outcome could be immediately included/
4. The discussion mentions regulatory bodies and post-marketing surveillance. Given that drugs like resmetirom have received approval based on surrogate endpoints, a brief discussion on the implications of this in the MASLD field would be very welcomed.
5. Please also ensure to double check that all references are following the guidelines prescribed by the journals

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper: “Comparative Safety and Efficacy of Resmetirom and Semaglutide in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review“ presents an interesting comparison of efficacy between resmetirom and semaglutide towards MASLD. It should be considered for publication after some issues are addressed:

1. The Introduction part requires additional information about MASLD nature of disease including the diagnostic criteria and differentiation form the alcoholic counterpart (ALD), as well as differences between lean patients with MASLD vs obese ones.
2. In the inclusion and exclusion criteria of the papers included in the review it should be emphasized whether there was limitation regarding the number of patients enrolled the stage of the disease, the doses of the medication or whether the studies chosen for further analysis had placebo (control) group.
3. Tables should be part of the Results and not the Discussion.
4. I do not understand the existence of Table 2 in comparison to Table 1. Why this two studies are not included in Table 1? If they are added to give overview of general characteristics of the drugs compared this table belongs rather to the Introduction part than to the Results.
5. If there was placebo group or control included it should be added as a column in the Table 1.
6. If there were any data regarding the values of waist circumference besides BMI as measurement of obesity; values of glucose levels/insulin levels/Hb1Ac; blood pressure values/ values of triglycerides and/or HDL since according diagnostic criteria the imabalances in these features together with liver fat make MASLD metabolically associated disease. If non of the study included this, please emphasize. It is given in Table 1 that there were somewhere data regarding BMI or the presence of diabetes, but that is two of five possible criteria - if there is data for other please add.
7. Besides limitations of the study, strengths should be added.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I would like to thank the authors for completing such extensive revisions. This draft now feels very elevated and should be accepted for publication.

I would also like to command the format of the revisions report, which makes our work as reviewers much easier - thank you.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have undertaken significant changes in the manuscript. However some minor points need to be addressed.

Minor comments

1. The reference number in the manuscript is 1 then 32 then 1-3. This should be revised
2. There some references in the text without number. For example: Loomba et al; Newsome et al. 
3. The numbers of the references need to be revised and should go by the order of appearance

Author Response

Please see the attachment.

Author Response File: Author Response.pdf