The authors are commended to adopt the BRAVO predictive model, having supra-conventional causation development capabilities, for their in-depth analyses exploring the long-term cardiovascular outcomes of Tirzepetide, a novel dual GIP-and-GLP-1 agonist, used for type-2 diabetes mellitus patients.

Despite the indirect estimation of short-term treatment effects of Insulin Glargine to those of Tirzepatide, the study has several undeniable limitations, as affirmed in the 'Discussion' section.

• Abstract
  Finely structured

• Introduction
  The authors are extolled for the efficient rationale development explored throughout the ‘Introduction’ section.

Better control of risk factors….. “has been noted to be associated with” (and not ‘was associated with’) lower risks of diabetes-related complications…..

• Methods
  The authors are recognized for their in-depth advanced analysis including developing ‘optimistic’ and ‘conservative’ scenarios.

It is suggested to stipulate the full form of abbreviations for the first time including that of MACE, ESRD and SPSL. It is also suggested to use the past tense throughout the manuscript.

• Results:
  The authors are acclaimed for their illustrative reporting of results, especially Figure 2 for its easy-to-understand, highly interpretive outlook. Figure 3 goes a step further and breaks down the contribution of each traditional variable towards the beneficial effects of Tirzepatide which is applauded.

P-values, shared as a column in Table 1, as well as throughout the ‘Results’ section including for numbers around symptomatic as well as severe hypoglycemia would help the readers to identify the statistically significant relations between variables.

Although the confidence intervals do assist in gauging the statistical significance, the authors are, nevertheless, suggested to share p-values, wherever possible.

• Supplementary Materials:
  The authors are commended for maintaining analyses transparency by sharing the analytical results in thier entirety.

• Discussion:
  The authors are commended for adequately explaining the narrow confidence interval of the effect of Tirzepatide on all-cause mortality

This is consistent with a previous study that found the reduction in HbA1c “explaining” (and not ‘explains’) 94.1% of the hazard reduction.
Giugliano D “et al.” (and not Giugliano, etc)
….. we predicted that the long-term use of tirzepatide…… may substantially reduce the risk….., compared to “that of” insulin glargine (and not ‘compared to insulin glargine’)

Regards.

The authors are extolled for the rationale development outlined in the ‘Introduction’ section, commended for their meticulous and transparent reporting of the adopted methodology and are recognised for their in-depth and fruit-bearing analysis that is possible because of their unwavering command over the subject matter.

Moreover, the comprehensiveness of the ‘Discussion’ section including but not limited to expounding the reason around a narrow confidence interval for the effect of Tirzepatide on the all-cause mortality is applauded.

Furthermore, the abstract is eulogized for its succinct all-inclusive note.

It is suggested to consider exploring proportional meta-analysis to determine the statistical significance of variations in the incidences of both: symptomatic hypoglycemia and severe hypoglycemia for the explored 4 arms.

On a supplementary note, it is suggested to define ‘severe hypoglycemia’.