Injectables Pharmacotherapies for Obesity: Mechanisms, Efficacy, and Aesthetic Implications
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
Marques Gomes et al. conducted a narrative review focused on different pharmacology strategies and the aesthetic problems derived from these treatments.
Please find some comments and suggestions that, in my opinion, could improve the manuscript:
Introduction
This section could be improved by adding some information regarding the aesthetic challenges of people with obesity that undergoes pharmacological interventions as the ones reviewed in this report.
Material and methods
Observational studies are not intervention studies. I think that the authors aimed to include only clinical studies. Please review and amend this point.
Which targeted keywords were used in PubMed for the literature search? Please clarify.
Please improve the grammar of the following sentence: “The selected studies which further Discussion below also served to build upon earlier works where data was presented in or before 2009 in the absence of more recently available studies”.
As the literature search strategy underwent changes, I recommend including a flowchart with the articles included in your review.
Literature review
Are there studies where the combination of weight-loss medications and the strategies to combat skin laxity were used?
It would be relevant to describe if the strategies to combat skin laxity have adverse effects or if there are some considerations for its use.
Discussion
This section is more a summary of the whole paper than an opinion of the authors on the topic of interest. I recommend redirecting this section towards an interpretation of the literature reviewed and highlight strengths and weaknesses on the topic.
Careful with these phrases as they do not seem appropriate: “facial laxity not only hurts the eye”.
Author Response
We thank the reviewers for their valuable suggestions and contributions to improving our manuscript. The issues raised have been carefully analyzed, and detailed responses to each comment are provided below.
1) This section could be improved by adding some information regarding the aesthetic challenges of people with obesity that undergoes pharmacological interventions as the ones reviewed in this report.
The text was revised to include the suggested information.
2) Observational studies are not intervention studies. I think that the authors aimed to include only clinical studies. Please review and amend this point.
The text was corrected.
3) Which targeted keywords were used in PubMed for the literature search? Please clarify.
The text was revised to include the suggested information.
4) Please improve the grammar of the following sentence: “The selected studies which further Discussion below also served to build upon earlier works where data was presented in or before 2009 in the absence of more recently available studies”.
The text was corrected.
5) As the literature search strategy underwent changes, I recommend including a flowchart with the articles included in your review.
We appreciate the suggestion to include a flowchart with the reviewed articles. However, the systematic searches conducted with descriptors and Boolean operators did not retrieve studies aligned with the scope of this work. For this reason, we opted to perform a non-systematic search for articles describing the mechanism of action of the active ingredients of interest and their use in obesity management. Consequently, the study was reformulated as a narrative review, which, unlike a systematic review, does not require the presentation of flowcharts as indicated by PRISMA.
6) Are there studies where the combination of weight-loss medications and the strategies to combat skin laxity were used?
An explanation was added to the text, indicating that there are no specific studies analyzing the mentioned combination but that there are reports of clinical efficacy evidenced by professionals in the field.
7) It would be relevant to describe if the strategies to combat skin laxity have adverse effects or if there are some considerations for its use.
Information added to the text.
8) This section is more a summary of the whole paper than an opinion of the authors on the topic of interest. I recommend redirecting this section towards an interpretation of the literature reviewed and highlight strengths and weaknesses on the topic.
The text was revised as suggested.
9) Careful with these phrases as they do not seem appropriate: “facial laxity not only hurts the eye”.
The text was revised as suggested.
Reviewer 2 Report
Comments and Suggestions for Authors1) Given that this review focuses on injectable medications for the treatment of obesity, it is recommended that the authors remove information pertaining to non-injectable medications, such as orlistat and mirabegron, as they fall outside the scope of the manuscript.
2) Additionally, the authors should incorporate information regarding emerging GLP-1 receptor agonists currently in phases 2–3 of clinical trials, such as survodutide and mazdutide.
The manuscript would benefit from the inclusion of strategies aimed at mitigating the gastrointestinal adverse effects associated with GLP-1 receptor agonists.
3) While Table 2 provides pharmacological details of active ingredients, it also includes findings that are not directly relevant to weight loss, which is the primary focus of this study. For example: “Vitamin B12, essential for energy metabolism and neurological function, increases mitochondrial energy production and corrects metabolic deficiencies associated with obesity, administered at doses of 2500 mcg intramuscularly weekly [41].” Such content appears tangential to the main objective of the manuscript.
4) As indicated by the title, this manuscript should emphasize advances in injectable pharmacotherapies for obesity. Consequently, the focus should be redirected from general active ingredients, as presented in Table 2, to data and findings from major clinical trials evaluating the efficacy of currently FDA/EMA-approved injectable drugs for obesity.
Furthermore, the authors should include a discussion on the long-term effects of these agents, as well as the outcomes and potential implications when the medication is discontinued.
Finally, it is important for the manuscript to address and discuss the critical role of lifestyle changes, such as diet and physical activity, in conjunction with these pharmacotherapies, as this topic is integral to the comprehensive management of obesity.
Comments on the Quality of English Language
Moderate English revision is needed.
Author Response
Since this review focuses on injectable medications for obesity treatment, the authors are advised to remove information about non-injectable drugs, such as orlistat and mirabegron, as they fall outside the manuscript's scope.
The text has been revised as suggested.
Additionally, the authors should incorporate information about emerging GLP-1 receptor agonists currently in phase 2 or 3 clinical trials, such as survodutide and mazdutide.
The text has been revised to include the suggested information.
The manuscript would benefit from the inclusion of strategies to mitigate gastrointestinal adverse effects associated with GLP-1 receptor agonists.
The text has been revised to include the suggested information.
Although Table 2 provides pharmacological details about the active ingredients, it also includes information not directly relevant to weight loss, which is the main focus of this study. For example: “Vitamin B12, essential for energy metabolism and neurological function, enhances mitochondrial energy production and corrects metabolic deficiencies associated with obesity, administered in doses of 2500 mcg intramuscularly weekly [41].” This content seems tangential to the manuscript's primary aim.
We appreciate the comment, however, we opted to retain the description of this substance in the table because, despite not directly aligning with the manuscript's objective, the action of this compound is used in combination therapies for weight management and loss. Therefore, its description is considered important for the readers.
As indicated by the title, this manuscript should emphasize advancements in injectable pharmacotherapies for obesity. Consequently, the focus should shift from general active ingredients, as presented in Table 2, to data and findings from major clinical trials evaluating the efficacy of injectable medications currently approved by the FDA/EMA for obesity.
Due to the difficulty of finding large clinical trials that specifically address advancements related to the use of the substances discussed in this manuscript for obesity management, the authors opted for a broader description of these compounds in the context of weight management and loss, rather than focusing exclusively on advancements. As a result, the manuscript title has been changed to: "Injectable Pharmacotherapies for Obesity: Mechanisms, Efficacy, and Aesthetic Implications."
Additionally, the authors should include a discussion about the long-term effects of these agents, as well as outcomes and potential implications when the medication is discontinued.
The text has been revised to include the suggested information.
Finally, it is important that the manuscript addresses and discusses the critical role of lifestyle changes, such as diet and physical activity, in conjunction with these pharmacotherapies, as this topic is essential for the comprehensive management of obesity.
The text has been modified to include the suggested information.
Author Response File: 
Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsThe article entitled Advances in Injectable Pharmacotherapies for Obesity: Mechanisms, Efficacy, and Aesthetic Implications represent a narrative review article aimed to summarize the most commonly used injectable pharmacotherapy in obesity treatment.
I introduction, there is a subsection Physiology of Obesity. It should be changed in Pathophysiology of obesity, and authors should describe the mechanisms that are involved in obesity development. It is important to point out the most significant mechanisms, since the therapy is directed towards these mechanisms that are described further in the text.
HMB abbreviation is missing full meaning where first mentioned.
If there are any data if there are advantages for using injections over oral therapy? In which situations?
Also, authors should mention llifestyle changes if they can improve the effects of injections.
Author Response
We thank the reviewers for their valuable suggestions and contributions to improving our manuscript. The issues raised have been carefully analyzed, and detailed responses to each comment are provided below.
1) Introduction, there is a subsection Physiology of Obesity. It should be changed in Pathophysiology of obesity, and authors should describe the mechanisms that are involved in obesity development. It is important to point out the most significant mechanisms, since the therapy is directed towards these mechanisms that are described further in the text.
The text was revised as suggested.
2) HMB abbreviation is missing full meaning where first mentioned.
The text was revised as suggested.
3) If there are any data if there are advantages for using injections over oral therapy? In which situations?
The text was revised to include the suggested information.
4) Also, authors should mention llifestyle changes if they can improve the effects of injections.
The text was revised to include the suggested information.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
thank you for considering my suggestions and comments.
I don't have further comments.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript still needs revision to be ready for publication. The title of the manuscript indicates that the authors will report medication to tackle obesity, however in their table 1 they report brand names that are not approved for obesity management such as Ozempic, which is a diabetes medicine used with diet and exercise to treat adults whose type 2 diabetes is not satisfactorily controlled.
My first comment "Since this review focuses on injectable medications for obesity treatment, the authors are advised to remove information about non-injectable drugs, such as orlistat and mirabegron, as they fall outside the manuscript's scope." has not been addressed by the authors even though they reported that they revised the text accordingly. However in Table 1 there are still non-injectable drugs.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsAuthors have revised the manuscript according to reviewer's suggestions. Manuscript has been significantly improved now.
Round 3
Reviewer 2 Report
Comments and Suggestions for AuthorsThe authors have addressed all my comments
