Reviewer's report
Title:A randomized, double-blind, placebo-controlled, multiple-dose
parallel-group clinical trial to assess the effects of teduglutide on gastric emptying
of liquids in healthy subjects
Version: 2Date:11 September 2013
Reviewer: Bolette Hartmann
Reviewer's report:
The authors investigated the effect of teduglutide on gastric emptying of liquids in
healthy subjects. The authors conclude that teduglutide does not delay
liquid-phase gastric emptying in healthy subjects.
The study is well conducted and well written. However there are some major
concerns.
1. First of all I wonder why the authors performed the study in healthy subjects.
The study would have been much more relevant if it had been performed in short
bowel patients.
2. p. 13, l 16-20: The conclusion doesn’t make sense and must be rewritten. This
finding is not relevant for SBS patients since the study is performed in healthy
subjects. It is true that “teduglutide is unlikely to modulate the bioavailability of
concomitant medications” –but this is in healthy subjects and healthy subjects will
not be treated with GLP-2……..
3. p. 9, l 18: A power analysis should be performed.
4. p. 10, l 7-12: I am not sure that the statistical analysis used is the most
appropriate. Would it be better to analyze data pair wise? Surely it would have
been more relevant to comparing Tmax at day 0 and at day 10 for each subject.
A statistician should be consulted regarding this question.
Minor points:
5. p. 3, l 5: “GLPs are derived from proglucagon and therefore may affect gastric
emptying…”. The meaning of this is unclear. Do the authors refer to the inhibitory
effect of GLP-1? This must be clarified.
6. p. 5, l 8: “…..the primary effects of GLP-2 are to regulate energy intake…” A
reference for this statement is needed.
7. p. 5, l 11: “..GLP-2 has limited effect on insulin secretion, glucagon
inhibition,….” Actually, GLP-2 has been shown to increase glucagon secretion
(Meier JJ et al, Gastroenterology 2006, p44-45).
8. p. 6, l 14: It is irrelevant to compare t½ for teduglutide after sc injection
(180-330min) with t½ for native GLP-2 after iv infusion (7min). The t½ for native
GLP-2 after sc injection is 1-1½h (Henriksen DB et al, Bone 2009, p833-842).
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:A randomized, double-blind, placebo-controlled, multiple-dose
parallel-group clinical trial to assess the effects of teduglutide on gastric emptying
of liquids in healthy subjects
Version: 2Date:11 September 2013
Reviewer: Bolette Hartmann
Reviewer's report:
The authors investigated the effect of teduglutide on gastric emptying of liquids in
healthy subjects. The authors conclude that teduglutide does not delay
liquid-phase gastric emptying in healthy subjects.
The study is well conducted and well written. However there are some major
concerns.
1. First of all I wonder why the authors performed the study in healthy subjects.
The study would have been much more relevant if it had been performed in short
bowel patients.
2. p. 13, l 16-20: The conclusion doesn’t make sense and must be rewritten. This
finding is not relevant for SBS patients since the study is performed in healthy
subjects. It is true that “teduglutide is unlikely to modulate the bioavailability of
concomitant medications” –but this is in healthy subjects and healthy subjects will
not be treated with GLP-2……..
3. p. 9, l 18: A power analysis should be performed.
4. p. 10, l 7-12: I am not sure that the statistical analysis used is the most
appropriate. Would it be better to analyze data pair wise? Surely it would have
been more relevant to comparing Tmax at day 0 and at day 10 for each subject.
A statistician should be consulted regarding this question.
Minor points:
5. p. 3, l 5: “GLPs are derived from proglucagon and therefore may affect gastric
emptying…”. The meaning of this is unclear. Do the authors refer to the inhibitory
effect of GLP-1? This must be clarified.
6. p. 5, l 8: “…..the primary effects of GLP-2 are to regulate energy intake…” A
reference for this statement is needed.
7. p. 5, l 11: “..GLP-2 has limited effect on insulin secretion, glucagon
inhibition,….” Actually, GLP-2 has been shown to increase glucagon secretion
(Meier JJ et al, Gastroenterology 2006, p44-45).
8. p. 6, l 14: It is irrelevant to compare t½ for teduglutide after sc injection
(180-330min) with t½ for native GLP-2 after iv infusion (7min). The t½ for native
GLP-2 after sc injection is 1-1½h (Henriksen DB et al, Bone 2009, p833-842).
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:A randomized, double-blind, placebo-controlled, multiple-dose
parallel-group clinical trial to assess the effects of teduglutide on gastric emptying
of liquids in healthy subjects
Version: 2Date:11 September 2013
Reviewer: Bolette Hartmann
Reviewer's report:
The authors investigated the effect of teduglutide on gastric emptying of liquids in
healthy subjects. The authors conclude that teduglutide does not delay
liquid-phase gastric emptying in healthy subjects.
The study is well conducted and well written. However there are some major
concerns.
1. First of all I wonder why the authors performed the study in healthy subjects.
The study would have been much more relevant if it had been performed in short
bowel patients.
2. p. 13, l 16-20: The conclusion doesn’t make sense and must be rewritten. This
finding is not relevant for SBS patients since the study is performed in healthy
subjects. It is true that “teduglutide is unlikely to modulate the bioavailability of
concomitant medications” –but this is in healthy subjects and healthy subjects will
not be treated with GLP-2……..
3. p. 9, l 18: A power analysis should be performed.
4. p. 10, l 7-12: I am not sure that the statistical analysis used is the most
appropriate. Would it be better to analyze data pair wise? Surely it would have
been more relevant to comparing Tmax at day 0 and at day 10 for each subject.
A statistician should be consulted regarding this question.
Minor points:
5. p. 3, l 5: “GLPs are derived from proglucagon and therefore may affect gastric
emptying…”. The meaning of this is unclear. Do the authors refer to the inhibitory
effect of GLP-1? This must be clarified.
6. p. 5, l 8: “…..the primary effects of GLP-2 are to regulate energy intake…” A
reference for this statement is needed.
7. p. 5, l 11: “..GLP-2 has limited effect on insulin secretion, glucagon
inhibition,….” Actually, GLP-2 has been shown to increase glucagon secretion
(Meier JJ et al, Gastroenterology 2006, p44-45).
8. p. 6, l 14: It is irrelevant to compare t½ for teduglutide after sc injection
(180-330min) with t½ for native GLP-2 after iv infusion (7min). The t½ for native
GLP-2 after sc injection is 1-1½h (Henriksen DB et al, Bone 2009, p833-842).
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
assistant