Title: Effect of Empagliflozin and Pioglitazone on Left Ventricular Function in Patients with
Type Two Diabetes and Nonalcoholic Fatty Liver Disease without Established Cardiovascular
Disease: A Randomized Single-blind Clinical Trial
Version: 1 Date: 04 Jan 2023
Reviewer's report:
Comments
The authors conducted the clinical trial to investigate the effect of pioglitazone and empagliflozin
on liver steatosis and fibrosis, and left ventricular function. There are several concerns to be
addressed.
Major
1. Study design in the method section. The authors should describe how the informed consent
of the participants were obtained.
2. Study design. The authors say this is double-blind trial but the patients can know which is
which by the shape and color of the compound using the web search? This reviewer thinks that
present study is single-blind test without placebo.
3. Discussion should be organized. Structure of the paragraphs is weird. For example, first
paragraph consists of only 2 sentences. Description about the mechanism of SGLT2 inhibitor
cites only one literature (about Santos-Gallego et al) but the paragraph for pioglitazone is too
long.
4. Sample size was calculated based on the previous paper (Akelbrom A, et al) which
investigated the GLS in T2DM, suggesting that sample size to test the effect on hepatic
pathogenesis of NAFLD is unclear. The authors described that 70 subjects were needed. Is it
for one group or total number of the subjects?
5. The authors should mention about the previous reports which investigated GLS or LV function
on T2DM with SGLT2 inhibitor and/or pioglitazone. Thinking about the high prevalence of
NAFLD in T2DM, advantage of the present study which included NAFLD patients with T2DM
is not so strong.
6. Overall, English editing by profession editor is mandatory.
Minor
1. Abstract, line 4 and overall. “P”ioglitazone ,“E”mpagliflozin. color “D”oppler There are
several capitalized first letter of the words in the sentences.
2. Abstract, line 7. Definition of “Active control”. Because the present study compared the effect
pioglitazone and empagliflozin, there is no appropriate control group. What does “active control”
mean?
3. All abbreviations in the main document should be spelled-out even though they are in the
abstract. Abstract is generally independent part in the manuscript.
4. Participant in the method section. Inclusion criteria and exclusion criteria should be
clearly described here. How was the “established” ASCVD was defined? Also, only ASCVD
was identified here rather than CVD? No limitation for age? How were the viral hepatitis,
autoimmune hepatitis and PBC/PSC excluded?
5. Procedure section is too long and need to be divided.
6. Outcomes measured in the method section. FIB-4 score should be FIB-4 index. NAFLD
fibrosis risk score is probably NAFLD fibrosis score? CAP score should be described as “CAP”
or “CAP measurement”.
7. Statistics. Please don’t use p=0.00. p < 0.01 or p < 0.001 is better.
8. Appendix 2 was not cited in the manuscript.
Title: Effect of Empagliflozin and Pioglitazone on Left Ventricular Function in Patients with
Type Two Diabetes and Nonalcoholic Fatty Liver Disease without Established Cardiovascular
Disease: A Randomized Single-blind Clinical Trial
Version: 1 Date: 04 Jan 2023
Reviewer's report:
Comments
The authors conducted the clinical trial to investigate the effect of pioglitazone and empagliflozin
on liver steatosis and fibrosis, and left ventricular function. There are several concerns to be
addressed.
Major
1. Study design in the method section. The authors should describe how the informed consent
of the participants were obtained.
2. Study design. The authors say this is double-blind trial but the patients can know which is
which by the shape and color of the compound using the web search? This reviewer thinks that
present study is single-blind test without placebo.
3. Discussion should be organized. Structure of the paragraphs is weird. For example, first
paragraph consists of only 2 sentences. Description about the mechanism of SGLT2 inhibitor
cites only one literature (about Santos-Gallego et al) but the paragraph for pioglitazone is too
long.
4. Sample size was calculated based on the previous paper (Akelbrom A, et al) which
investigated the GLS in T2DM, suggesting that sample size to test the effect on hepatic
pathogenesis of NAFLD is unclear. The authors described that 70 subjects were needed. Is it
for one group or total number of the subjects?
5. The authors should mention about the previous reports which investigated GLS or LV function
on T2DM with SGLT2 inhibitor and/or pioglitazone. Thinking about the high prevalence of
NAFLD in T2DM, advantage of the present study which included NAFLD patients with T2DM
is not so strong.
6. Overall, English editing by profession editor is mandatory.
Minor
1. Abstract, line 4 and overall. “P”ioglitazone ,“E”mpagliflozin. color “D”oppler There are
several capitalized first letter of the words in the sentences.
2. Abstract, line 7. Definition of “Active control”. Because the present study compared the effect
pioglitazone and empagliflozin, there is no appropriate control group. What does “active control”
mean?
3. All abbreviations in the main document should be spelled-out even though they are in the
abstract. Abstract is generally independent part in the manuscript.
4. Participant in the method section. Inclusion criteria and exclusion criteria should be
clearly described here. How was the “established” ASCVD was defined? Also, only ASCVD
was identified here rather than CVD? No limitation for age? How were the viral hepatitis,
autoimmune hepatitis and PBC/PSC excluded?
5. Procedure section is too long and need to be divided.
6. Outcomes measured in the method section. FIB-4 score should be FIB-4 index. NAFLD
fibrosis risk score is probably NAFLD fibrosis score? CAP score should be described as “CAP”
or “CAP measurement”.
7. Statistics. Please don’t use p=0.00. p < 0.01 or p < 0.001 is better.
8. Appendix 2 was not cited in the manuscript.
Please review this paper.
user
Title: Effect of Empagliflozin and Pioglitazone on Left Ventricular Function in Patients with
Type Two Diabetes and Nonalcoholic Fatty Liver Disease without Established Cardiovascular
Disease: A Randomized Single-blind Clinical Trial
Version: 1 Date: 04 Jan 2023
Reviewer's report:
Comments
The authors conducted the clinical trial to investigate the effect of pioglitazone and empagliflozin
on liver steatosis and fibrosis, and left ventricular function. There are several concerns to be
addressed.
Major
1. Study design in the method section. The authors should describe how the informed consent
of the participants were obtained.
2. Study design. The authors say this is double-blind trial but the patients can know which is
which by the shape and color of the compound using the web search? This reviewer thinks that
present study is single-blind test without placebo.
3. Discussion should be organized. Structure of the paragraphs is weird. For example, first
paragraph consists of only 2 sentences. Description about the mechanism of SGLT2 inhibitor
cites only one literature (about Santos-Gallego et al) but the paragraph for pioglitazone is too
long.
4. Sample size was calculated based on the previous paper (Akelbrom A, et al) which
investigated the GLS in T2DM, suggesting that sample size to test the effect on hepatic
pathogenesis of NAFLD is unclear. The authors described that 70 subjects were needed. Is it
for one group or total number of the subjects?
5. The authors should mention about the previous reports which investigated GLS or LV function
on T2DM with SGLT2 inhibitor and/or pioglitazone. Thinking about the high prevalence of
NAFLD in T2DM, advantage of the present study which included NAFLD patients with T2DM
is not so strong.
6. Overall, English editing by profession editor is mandatory.
Minor
1. Abstract, line 4 and overall. “P”ioglitazone ,“E”mpagliflozin. color “D”oppler There are
several capitalized first letter of the words in the sentences.
2. Abstract, line 7. Definition of “Active control”. Because the present study compared the effect
pioglitazone and empagliflozin, there is no appropriate control group. What does “active control”
mean?
3. All abbreviations in the main document should be spelled-out even though they are in the
abstract. Abstract is generally independent part in the manuscript.
4. Participant in the method section. Inclusion criteria and exclusion criteria should be
clearly described here. How was the “established” ASCVD was defined? Also, only ASCVD
was identified here rather than CVD? No limitation for age? How were the viral hepatitis,
autoimmune hepatitis and PBC/PSC excluded?
5. Procedure section is too long and need to be divided.
6. Outcomes measured in the method section. FIB-4 score should be FIB-4 index. NAFLD
fibrosis risk score is probably NAFLD fibrosis score? CAP score should be described as “CAP”
or “CAP measurement”.
7. Statistics. Please don’t use p=0.00. p < 0.01 or p < 0.001 is better.
8. Appendix 2 was not cited in the manuscript.
assistant