Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 1 Date: 05 Jul 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Re: Comparative Effectiveness of Individual GLP-1 Receptor Agonists on Colorectal Cancer
Risk: A Meta-Analysis of Retrospective Cohort Studies
Dear Authors,
Thank you for the submission. While the study addresses an important clinical concern, I regret
that I am unable to recommend it for publication in its current form.
The central limitation lies in the inconsistency and, in several cases, insufficiency of follow-
up durations across the included studies. Drawing conclusions about colorectal cancer risk—
particularly a significantly elevated risk—from retrospective cohorts with follow-up as short as
six months is methodologically unsound. Cancer development requires long latency, and such
short windows undermine the credibility of the association.
Furthermore, the exposure was not stratified by agent or duration, limiting biological
interpretability. The distinction between risk and incidence is inconsistently handled, and the
non-significant, heterogeneous incidence data further weakens the case. Although the PRISMA
framework is followed, the inclusion of such short-term studies fundamentally limits the meta-
analysis.
In its current form, the conclusions overreach the evidence base. I would recommend a more
conservative and methodologically rigorous approach in future work, ideally incorporating
prospective data with well-defined exposure windows and cancer latency considerations.
Sincerely,
Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 1 Date: 05 Jul 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Re: Comparative Effectiveness of Individual GLP-1 Receptor Agonists on Colorectal Cancer
Risk: A Meta-Analysis of Retrospective Cohort Studies
Dear Authors,
Thank you for the submission. While the study addresses an important clinical concern, I regret
that I am unable to recommend it for publication in its current form.
The central limitation lies in the inconsistency and, in several cases, insufficiency of follow-
up durations across the included studies. Drawing conclusions about colorectal cancer risk—
particularly a significantly elevated risk—from retrospective cohorts with follow-up as short as
six months is methodologically unsound. Cancer development requires long latency, and such
short windows undermine the credibility of the association.
Furthermore, the exposure was not stratified by agent or duration, limiting biological
interpretability. The distinction between risk and incidence is inconsistently handled, and the
non-significant, heterogeneous incidence data further weakens the case. Although the PRISMA
framework is followed, the inclusion of such short-term studies fundamentally limits the meta-
analysis.
In its current form, the conclusions overreach the evidence base. I would recommend a more
conservative and methodologically rigorous approach in future work, ideally incorporating
prospective data with well-defined exposure windows and cancer latency considerations.
Sincerely,
Please review this paper.
user
Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 1 Date: 05 Jul 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Re: Comparative Effectiveness of Individual GLP-1 Receptor Agonists on Colorectal Cancer
Risk: A Meta-Analysis of Retrospective Cohort Studies
Dear Authors,
Thank you for the submission. While the study addresses an important clinical concern, I regret
that I am unable to recommend it for publication in its current form.
The central limitation lies in the inconsistency and, in several cases, insufficiency of follow-
up durations across the included studies. Drawing conclusions about colorectal cancer risk—
particularly a significantly elevated risk—from retrospective cohorts with follow-up as short as
six months is methodologically unsound. Cancer development requires long latency, and such
short windows undermine the credibility of the association.
Furthermore, the exposure was not stratified by agent or duration, limiting biological
interpretability. The distinction between risk and incidence is inconsistently handled, and the
non-significant, heterogeneous incidence data further weakens the case. Although the PRISMA
framework is followed, the inclusion of such short-term studies fundamentally limits the meta-
analysis.
In its current form, the conclusions overreach the evidence base. I would recommend a more
conservative and methodologically rigorous approach in future work, ideally incorporating
prospective data with well-defined exposure windows and cancer latency considerations.
Sincerely,
assistant