Evaluation of Clinical and Quality of Life Effects of Oral Semaglutide Use in Type 2 Diabetes from a Public Health View: A Prospective Study in Italy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review Report: Diabetology (MDPI)

Journal: Diabetology (ISSN 2673-4540)

Manuscript ID: diabetology-3698164

 

Title:  Evaluation of Clinical and Quality of Life Effects of Oral Semaglutide Use in Type 2 Diabetes on Public Health View: A Prospective Study in Italy

Authors:  Paola Pantanetti et al.,

Overall comment: GLP1 inhibitors are now the talk of the town in diabetes research, with numerous pros. And conc. However, the author attempted to portray the significance and efficacy of oral Semaglitide over injectable one, using the application of QoL, and a new approach, no doubt. This reviewer finds some difficulty in comparing the efficacies over the injectable form as one arm of the experimental group, the main concern, which dampens the spirit of the manuscript; however, commendable work is included. A few other specific concerns are below:

 

Specific Comments:

In Abstract

Line 40: The term provided is not a good term in this sense. You don’t get the full results for all the participants for any reason they're off. That is quite common. Use a different phrase or say, “ 97 participants have the complete and …..”.

Line 42: for p value, should provide a symbol and say significant as the value represents, and should have the range in between. As of now, this is a p-value with the significance ≤ 0.005 (0.0028 -????).

Line 42: “Patient-reported outcome ….”. Doesn’t sound good.  Need a language correction.

Line 49 (Keywords): Consider QoL in place of real-life practice. That fits more.

In Introduction

Line 98: What is NEW? There has been a lot of information on it.

See https://pubmed.ncbi.nlm.nih.gov/39316289/.

Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial. And  Ishii H, Hansen BB, Langer J, Horio H. Diabetes Ther. 2021 Feb;12(2):613-623. doi: 10.1007/s13300-020-00985-w. Epub 2021 Jan 18.

How can you differentiate from the others? Is your QoL a new concept?  What aspect of injectable vs. oral was considered in the patient's improvement? (This was the main concern).

Line 104: “Validated tools? Should have the references and name a few in the parentheses as they first appear. Even though the author mentions them later.

Line 121-129: Not in a bulleted format. Describe them in a smart, continuous text.

Line 161: Mention the text reference of the supplementary files that it relates to and the references, if any, in the parentheses.

Line 207: Figure 1 should be concise to reduce the space. Unnecessary big. And should come under he materials and methods and should refer to that.

Line 208: Move the Table 1 text to the next page (a technical one).

Line 215: “ Clinical -metabolic results”. This is not a good clinical statement (say, metabolic panel results demonstrate that we know, all are clinical (biochemistry we call it sometimes) results.

In Discussion:  

Line 273-274: Were they statistically significant? Also, put the value of significance and the range of the data in parentheses for each parameter.  

Line 333-334: This is the major and serious concern, which lacks a treatment group that should have received an injectable form, to compare with. Find out a solution either from published data or with a comparative arm in place.  

Author Response

Dear Peer,

thank you again for your effort and kind collaboration.

The Authors

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This study investigated the effects of oral semaglutide in 97 patients over a period of 18 months (a so-called real-world study). In addition to some objective criteria, such as certain blood values (clinical outcomes), the study focuses primarily on interviewing patients and their satisfaction with the therapy. The lack of control groups or comparator groups as well as the small number of study participants are limitations, but these are correctly mentioned.

Unfortunately, this means that the results can only be generalized to a limited extent. However, this has already been mentioned in the Limitations section.

I have just a few concerns:

1. The results of the clinical parameters at the examination times must also be given, and not only the basal parameters and the statistical evaluation of the changes. This allows the reader to better classify the results.
2. What side effects of oral semaglutide have been reported by the patients (if any)? This must also be mentioned.
3. The eight items of the WHO DTSQ questionnaire must be explained in the main text, as has been done in Table 4 for the SF-36 domains.
4. Please check whether the numerous references are really relevant for this research.

Author Response

Dear Peer,

thank you again for your effort and kind disponibility.

Best

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thanks autors for taking care of the requested applicable measures, that now looks accpetable. Good work indeed.

Author Response

Dear Peer,

thank you again for your time and efforts.

Have you a nice day.

The Authors

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have responded appropriately to my concerns.

I would just like to comment on their response to point 1 of my original concerns:

I understand that the authors want to avoid unnecessary redundancies. Especially since these additional data would not change the message of the study. Nevertheless, interested readers and researchers active in this field would be interested in seeing the raw data. This could be accomplished by including the data as an online supplement.

Author Response

Dear Peer,

thank you again for your effots and time.

We would like to sincerely thank the Reviewer for the attention, thoughtfulness, and interest shown in our work. We truly appreciate the comment regarding the potential availability of the raw data, and we fully recognize the value of open science and data transparency within the research community. However, we wish to clarify that, during the data collection phase, patients provided informed consent exclusively for the scientific use of their data in aggregated and anonymized form. The consent form—drafted in accordance with the highest ethical standards—did not include any reference to the possibility of sharing individual-level data, even in anonymized form. As researchers, we believe it is our ethical duty to fully respect the conditions agreed upon with participants. Additionally, the data analyzed in our study were obtained from corporate sources and are subject to specific confidentiality and ownership constraints. Any dissemination, even for scientific purposes, must be explicitly authorized by the relevant companies. In the Italian context, unauthorized sharing of corporate or health-related data may lead to significant implications—not only from an ethical standpoint but also from a disciplinary and legal perspective—under current regulations governing privacy, data protection, and the handling of proprietary or sensitive healthcare information. That said, we are truly grateful to the Reviewer for raising this important point. The suggestion has also helped us identify and correct a material error in the "Data Availability Statement", which had unintentionally indicated that the data would be accessible online. We have revised the statement as follows:

"The data analyzed in this study were provided in aggregated form by corporate sources and cannot be publicly shared due to ethical, contractual, and legal constraints. Specific data access requests may be considered on a case-by-case basis, subject to authorization by the relevant companies. The corresponding authors may act as intermediaries to facilitate contact with the data owners and assess the feasibility of such requests, in full compliance with applicable regulations".

In conclusion, we once again thank the Reviewer not only for the thoughtful comment but also for providing a valuable opportunity to improve the clarity and rigor of our manuscript. We are committed to incorporating this suggestion in future research projects—both prospective and retrospective—by explicitly including the option for data sharing in the informed consent process, with the aim of fostering collaboration and openness within the scientific community. Your recommendation will serve as an important reference for us moving forward.

Thenk you again and we hope to full answer your comment.