This is a reasonably comprehensive narrative review giving the rationale for and interpretations of results of recent pharma trials of the weekly market-leading GLP-1 RA agents dulaglutide and semaglutide. It does not add much to other recent narrative reviews that have been published except some discussion of the recent development of non-peptide GLP1-RAs.

Major

1) No description of literature search methods used
2) No conflicts of interest provided
3) Little discussion of guidelines/ positioning in relation to other available and forthcoming agents (e.g. dual agonists)
4) Very little detail on mechanistic aspects e.g. for rise in pulse rate, decreased satiety
5) Figures or tables could have been useful for summarising information - not provided
6) The explanation of why the SOUL trial was restarted given the FDA view is confusing. It is also stated that a CVOT "was never undertaken" for semaglutide once weekly formulation but then that SOUL and SELECT trial are in progress.
7) The Conclusion repeats too much of what was already stated. It is incorrect to say that there are "no safety concerns" when there are ongoing trials to establish retinal safety (also there is a clear excess of cholelithiasis/ cholecystitis with both agents).
8) Too much extrapolation in the Conclusions in relation to retinal and cardiovascular safety e.g. "we feel that this represents," "this concern should be resolved" and "a similar outcome is almost certain for semaglutide."

Minor
1) Should state that standard release exenatide was launched in 2006
2) Should be made clearer that reason for the recent FDA refusal of the application for a 2.0 mg dose of semaglutide was not made on the basis of any clinical data submitted.
3) Co-primary endpoints of STEP trials should be stated explicitly
4) Absolute rates of retinopathy with dulaglutide should be stated (as they are for semaglutide)
5) HbA1c does not need a decimal place when expressed as mmol/L
6) "Legitimised" is an odd word choice to describe the implications of the FDA view - "supported"?
7) "Smoothed" is rather a colloquial term to describe the pharmacokinetics of oral semaglutide
8) Use on at least two occasions of the formulation "trial x was the CVOT for drug y" implies that commissioning of a single CVOT is the only possible regulatory paradigm that could have existed (rather than the one that is currently in place)