The study by Arnott et al. aimed to determine whether the effect of canagliflozin on the composite of HHF/CV death differs in subgroups defined by key baseline participant characteristics that are associated with incident heart failure and its attendant complications.

The authors used Cox regression models to estimate hazard ratios and 95% confidence intervals.

The authors showed that reducing the relative risk of HHF/CV death with canagliflozin treatment is independent on age, sex, history of heart failure or CV disease, baseline eGFR, UACR, or the use of loop diuretics.

The study analysis also showed that canagliflozin's absolute benefit was greater in those at the highest baseline risk, such as those with CV disease or advanced kidney disease.

The authors concluded that Patients with co-existent diabetes and CKD are at a high risk of HHF/CV death events, and canagliflozin consistently reduces the proportional risk of these events across a broad range of subgroups.

The study is well-designed, and the manuscript is well-written. The topic is of interest to the readership of Diabetes, Obesity and Metabolism. I have a few suggestions to improve the clarity and quality of the manuscript.

Major concerns:

1- How are these results compared to other clinical trials where empagliflozin was used instead of canagliflozin?

2- The discussion regarding the mechanism through which SGLT2 inhibitors are mediating their cardoprotection should be developed further.

3- The main concluding points of the study need to be added to the abstract.

4- The first sentence in the introduction needs to be supported by a reference!

The authors have adequately addressed my concerns and comments. Thank you!