Title: Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. DOM-22-0122-OP

Thanks for the opportunity to review this study.

The study discusses relatively important questions about weight regain, cardiovascular variables, and glycemic status after semaglutide withdrawal after being supplemented for a relatively long period.

This exploratory study represents an extension phase of the step 1 trial. The authors conducted the trial well, and the conclusion supports the results.

I have some minor revisions:

The introduction had been conducted well, stating the background and posting the aim clearly.

For the methods section:

Line 107: it would be easier for the reader to not confuse with other coexisting conditions (table 1), to state the obesity-related comorbidity as mentioned in STEP 1 trial "hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease".

Line 111: it would also be easier for the reader to mention how the lifestyle intervention was, as written in the legend of figure S1.

Line 126, 127: the authors state that the participants were eligible with the same eligibility criteria of the main phase, excluding the diabetic population. However, in figure 3, three diabetic patients in the placebo arm had entered the extension phase. You, the authors, could widen the eligibility for the extension phase.

For the results section:

Table 1: in the footnote, regarding the symbol "¶". The authors pointed to a history of some diseases such as cerebrovascular disease, impaired glucose metabolism, kidney disease, gout, and thyroid disease and did not mention their incidence among included populations in the table. If there were no records for them, you might delete them from the footnote.

Table S3: not many people understand the significance by a confidence interval. You can add the P-value of significance for those differences if possible.

Table S4: in the footnote, a reference for glycemic categorization is 21, not one; please amend it.

The discussion summarized the findings well but needed a broader view adding a subsection explaining the results of subgroups based on the participants’ characteristics.

Finally, the conclusion answered the question and supported the results.

Overall, the study was conducted well and will be suitable for publication after revising the notes as mentioned above.

ALSO SEE ATTACHED DOCUMENT

I want to thank the authors for their edits based on the comments I have provided. Regarding comment 6, I meant table S2, and it's ok to apply the confidence range rather than one point significance (p-value). In comment 7, I understand and agree for sure.
In general, the paper has been conducted well, providing original results. I have my thoughts regarding the number, but for exploratory analysis, it's accepted.
Thank you and good luck