Title: Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal
regenerative effects in an experimental model of inflammatory bowel disease in rats
Version: 1 Date: 19 Nov 2022
Reviewer's report:
The present paper aims to  investigate the therapeutical benefits of glepaglutide, a long acting
GLP-2 analogue,  in rats with small intestinal inflammation.
I would like to thank the authors for  conducting this study which supports a different approach
to dealing with inflammatory bowel disease. The authors may wish to consider the following
comments
General comments
The paper is well written. However, many sentences are too long making it difficult for the
reader to follow the point.
I am not sure about the value of the long and detailed Table 1 and 2  which are rather confusing
and do not add to the reader’s understanding. Consider deleting or communicating in a more
comprehensive way.
Specific comments
Page 3, line 72-73: Alle IBD therapies aim to improve intestinal barrier function which is usually
evident by histological remission. This is true about Prednisolon (PMID: 33575854), infliximab
(PMID: 22398062) as well as other biologics.
Page 6,  line 148:  Which markers were used to ensure that inflammation was stablished? How
fast can one expect the inflammation would take place after administration of INDO?
Pages 7-8, lines 170-177: Is the method validated? If so, please include a reference.
Page 10,  line 233:  How many rats were used in each arm? Please include a figure with
study design clearly showing each arm, number of rats included, duration of study and study
termination.
Page 10, line 234: Was a dose-dependency test run? Please include a p-value.
Page 10, line 242: Were there any side effects? Or did everything go as planned?
Page 11, line 263, tabel 1: should the unit not be % since it is relative to body weight?
Page 13, lines 300-3001: How can the authoers claim that glepaglutide induced trophicity
7 days after dosing ,all based on intestinal weight? No biopsies were taken and no
immunohistochemistry analyses were performed. Couldn’t it just be an increased intestinal
blood flow resulting in an increased intestinal weight?
Page 15, lines 335-338: GLP-2 is a potent intestinotrophic agent. Should we be concerned (more
than we already are in "healthy" intestine) about its usage in an inflamed environment with a
rapid cell turnover and possibility and risk for mutations and malignancy?
Page 15, lines 347-348: see comment on page 3. Prednisolone is a potent agent inducing mucosal
healing.
Title: Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal
regenerative effects in an experimental model of inflammatory bowel disease in rats
Version: 1 Date: 19 Nov 2022
Reviewer's report:
The present paper aims to  investigate the therapeutical benefits of glepaglutide, a long acting
GLP-2 analogue,  in rats with small intestinal inflammation.
I would like to thank the authors for  conducting this study which supports a different approach
to dealing with inflammatory bowel disease. The authors may wish to consider the following
comments
General comments
The paper is well written. However, many sentences are too long making it difficult for the
reader to follow the point.
I am not sure about the value of the long and detailed Table 1 and 2  which are rather confusing
and do not add to the reader’s understanding. Consider deleting or communicating in a more
comprehensive way.
Specific comments
Page 3, line 72-73: Alle IBD therapies aim to improve intestinal barrier function which is usually
evident by histological remission. This is true about Prednisolon (PMID: 33575854), infliximab
(PMID: 22398062) as well as other biologics.
Page 6,  line 148:  Which markers were used to ensure that inflammation was stablished? How
fast can one expect the inflammation would take place after administration of INDO?
Pages 7-8, lines 170-177: Is the method validated? If so, please include a reference.
Page 10,  line 233:  How many rats were used in each arm? Please include a figure with
study design clearly showing each arm, number of rats included, duration of study and study
termination.
Page 10, line 234: Was a dose-dependency test run? Please include a p-value.
Page 10, line 242: Were there any side effects? Or did everything go as planned?
Page 11, line 263, tabel 1: should the unit not be % since it is relative to body weight?
Page 13, lines 300-3001: How can the authoers claim that glepaglutide induced trophicity
7 days after dosing ,all based on intestinal weight? No biopsies were taken and no
immunohistochemistry analyses were performed. Couldn’t it just be an increased intestinal
blood flow resulting in an increased intestinal weight?
Page 15, lines 335-338: GLP-2 is a potent intestinotrophic agent. Should we be concerned (more
than we already are in "healthy" intestine) about its usage in an inflamed environment with a
rapid cell turnover and possibility and risk for mutations and malignancy?
Page 15, lines 347-348: see comment on page 3. Prednisolone is a potent agent inducing mucosal
healing.
Please review this paper.
user
Title: Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal
regenerative effects in an experimental model of inflammatory bowel disease in rats
Version: 1 Date: 19 Nov 2022
Reviewer's report:
The present paper aims to  investigate the therapeutical benefits of glepaglutide, a long acting
GLP-2 analogue,  in rats with small intestinal inflammation.
I would like to thank the authors for  conducting this study which supports a different approach
to dealing with inflammatory bowel disease. The authors may wish to consider the following
comments
General comments
The paper is well written. However, many sentences are too long making it difficult for the
reader to follow the point.
I am not sure about the value of the long and detailed Table 1 and 2  which are rather confusing
and do not add to the reader’s understanding. Consider deleting or communicating in a more
comprehensive way.
Specific comments
Page 3, line 72-73: Alle IBD therapies aim to improve intestinal barrier function which is usually
evident by histological remission. This is true about Prednisolon (PMID: 33575854), infliximab
(PMID: 22398062) as well as other biologics.
Page 6,  line 148:  Which markers were used to ensure that inflammation was stablished? How
fast can one expect the inflammation would take place after administration of INDO?
Pages 7-8, lines 170-177: Is the method validated? If so, please include a reference.
Page 10,  line 233:  How many rats were used in each arm? Please include a figure with
study design clearly showing each arm, number of rats included, duration of study and study
termination.
Page 10, line 234: Was a dose-dependency test run? Please include a p-value.
Page 10, line 242: Were there any side effects? Or did everything go as planned?
Page 11, line 263, tabel 1: should the unit not be % since it is relative to body weight?
Page 13, lines 300-3001: How can the authoers claim that glepaglutide induced trophicity
7 days after dosing ,all based on intestinal weight? No biopsies were taken and no
immunohistochemistry analyses were performed. Couldn’t it just be an increased intestinal
blood flow resulting in an increased intestinal weight?
Page 15, lines 335-338: GLP-2 is a potent intestinotrophic agent. Should we be concerned (more
than we already are in "healthy" intestine) about its usage in an inflamed environment with a
rapid cell turnover and possibility and risk for mutations and malignancy?
Page 15, lines 347-348: see comment on page 3. Prednisolone is a potent agent inducing mucosal
healing.
assistant