The study is of interest as investigating relatively novel compound and provides some useful data in an asian study population. Sample size is small in some groups.

Generally the writing is a little vague, leaving the reader constantly needing to look up other studies to evaluate the data. For example, as the comparison with other study populations is the differentiating feature, can this be discussed more specifically with numbers rather than general descriptions using words like 'comparable' so that the reader doesn't have to look up the relevant data?

Similarly with pulse rate increase (eg +8 bpm 95%CI, likely reactive due to fall in BP) and quoting the weight loss over the equivalent period with GLP-1 alone treatment so that the reader has some idea of how the two compounds might compare with regards to weight loss and to improvement in glycemia.

Minor
Abstract Line 43 (and perhaps in page 12 line 40) Can the difference with 95% CI be presented for each dose vs placebo.

Page 4 line 30 - can an indication of the relative agonism at each receptor of this compound be indicated and a brief sentence stating the expected additional benefits of co-agonism vs GLP-1 alone?

Figure S2 Is there a relationship between body weight and cotadutide level at the different doses ? As in, could dosing benefit from adjustment for weight?

Figure S3 can these graphs be presented as scatter dot plots to show individual data points in addition to the mean? It's traditional to present the placebo or control group as the first column.

Table S5 the HbA1c fall seems less in the 300 mcl group. The statistical difference presented is vs baseline, but is there any difference between the groups? Can the authors discuss recommend dosing for clinical use based on this data. Why was no multiplicity adjustment not done to enable comparison between groups?