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Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.

Name: Adcurare Rigor Record — Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.
Item: Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.
Rating: 100
Author: Adcurare

Malhotra A, Grunstein R, Azarbarzin A, Sands S, Somers VK, Aronne LJ, Jastreboff AM, Lou J, Chakladar S, Dunn JP, Bunck MC, Bednarik J

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Adcurare Rigor Review — 5★ (Exemplary), 0 critical, 4 high issues for “Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 7, 2026

Adcurare Rigor Review

Rigor Reviewed

5 / 5

Exemplary — no material problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — no deductions. Nothing the checks ran surfaced a material problem.

Model-reported confidence: highReviewer agreement: moderateEngine: 7.6.0Source: full text

Not verified in this report

No reported statistical tests were found to recompute.

No specific rigor problems surfaced by the checks that ran.

This Adcurare Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper reports secondary analyses from two well-conducted phase 3 RCTs, with a clear scientific premise, robust study design, and transparent reporting. The main methodological weakness is in the statistical analysis dimension, where assumptions are not explicitly verified and effect sizes for some outcomes lack confidence intervals.

All eight dimensions were applicable and evaluated. The reviewers agreed on seven dimensions; the statistical analysis dimension had a split (pass vs. warn), resolved to 'warn' based on specific reporting gaps. The statistics verification component could not recompute any tests due to insufficient reported detail (no test statistics with df or effect + CI for all outcomes).

12 major claims checked against the paper's own evidence: all adequately supported.

Reporting

Eight Dimensions8 pass

The introduction cites prior work on the relationship between OSA and cardiovascular risk, the limitations of PAP therapy (inconsistent cardiovascular outcomes, adherence issues), and the known effects of tirzepatide on weight and glucose control (refs 8-10). It explicitly states the gap: 'The results lead to questions about how much of the cardiometabolic benefits associated with tirzepatide are related to improvement in OSA severity per se versus improvement in body weight.' The hypothesis and objectives follow from this gap. The limitations of prior research are addressed indirectly through the study design (prospective, randomized, controlled, mediation analysis).

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific premise: OSA and obesity are linked, prior PAP trials have shown inconsistent cardiovascular benefits, and tirzepatide reduces weight and AHI. The rationale for examining cardiometabolic risk measures and mediation analysis is logical and directly follows from cited evidence.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“The introduction cites 13+ references covering OSA epidemiology, PAP limitations, obesity as a risk factor, and tirzepatide's prior efficacy on weight and glucose.”

direct quote[Introduction, paragraph 3, sentence 7]

“The results lead to questions about how much of the cardiometabolic benefits associated with tirzepatide are related to improvement in OSA severity per se versus improvement in body weight.”

direct quote[Introduction, paragraph 4]

“Based on this conceptual framework and including a complete set of study prespecified cardiometabolic endpoints, we sought to test the hypothesis that tirzepatide treatment in the SURMOUNT-OSA studies would yield improvement in cardiometabolic risk measures as compared to placebo.”

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise by citing prior research on OSA, obesity, and tirzepatide, and provides a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“The introduction cites prior studies on OSA, obesity, PAP therapy limitations, and tirzepatide's effects on weight and glucose control.”

direct quote[Introduction, paragraph 1]

“PAP has not shown consistent benefits in patients with OSA from the perspective of cardiovascular outcomes.”

direct quote[Introduction, paragraph 4]

“we sought to test the hypothesis that tirzepatide treatment in the SURMOUNT-OSA studies would yield improvement in cardiometabolic risk measures as compared to placebo.”

PASSReviewer 3· 95% conf

The scientific premise is well established through citation of prior research on OSA, obesity, and tirzepatide, with a clear logical rationale for the study hypotheses.

Evidence

direct quote[Introduction, paragraphs 1-4]

“Obstructive sleep apnea (OSA) is a common disorder with major cardiometabolic and neurocognitive sequelae.”

direct quote[Introduction, paragraph 5]

direct quote[Introduction, paragraph 1]

“Moreover, PAP has not shown consistent benefits in patients with OSA from the perspective of cardiovascular outcomes.”

Randomization (1:1 ratio) and double-blinding are stated. The unit of randomization is the individual participant. Inclusion/exclusion criteria are referenced from the published primary papers. A statistical analysis plan prespecified most endpoints. The efficacy estimand and multiple imputation for missing data are described. Power analysis is not reported in this paper but is implied from the primary studies. The mediation analysis and the HOMA-IR analysis are post-hoc/exploratory, which is transparently acknowledged.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is robust: two randomized, double-blind, placebo-controlled phase 3 trials with clearly described randomization, blinding, inclusion/exclusion criteria, and a pre-specified statistical analysis plan for the primary and key secondary endpoints. The mediation analysis and post-hoc HOMA-IR analysis are clearly described but not pre-specified.

Evidence

direct quote[Methods, paragraph 1]

“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”

direct quote[Abstract and Methods]

“two, 52-week, randomized, double-blind, placebo-controlled phase 3 studies”

direct quote[Methods, paragraph 1]

“The SURMOUNT-OSA program was registered at ClinicalTrials.gov (NCT05412004), and the two studies' full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously.”

PASSReviewer 2· 95% conf

The study design is rigorous: randomized, double-blind, placebo-controlled, with adequate inclusion/exclusion criteria and prespecified outcomes.

Evidence

direct quote[Methods, Study design, procedures and participants, paragraph 1]

“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”

direct quote[Abstract, paragraph 1]

“The SURMOUNT-OSA master protocol comprised two, 52-week, randomized, double-blind, placebo-controlled phase 3 studies”

paraphrase[Methods, paragraph 1]

“The full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously.”

PASSReviewer 3· 90% conf

The study design is rigorous: it is a pre-specified secondary analysis of two randomized, double-blind, placebo-controlled trials with adequate reporting of randomization, blinding, and pre-specified endpoints.

Evidence

direct quote[Abstract]

“The SURMOUNT-OSA master protocol comprised two, 52-week, randomized, double-blind, placebo-controlled phase 3 studies (study 1 and study 2)”

direct quote[Methods, first paragraph]

“The SURMOUNT-OSA program was registered at ClinicalTrials.gov (NCT05412004), and the two studies’ full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously”

direct quote[Methods, Statistical analysis]

“The changes in HOMA-IR were analyzed post hoc.”

The methods state participants were screened 'irrespective of their sex' and that sex was self-reported. Baseline demographics are referenced to a table (Extended Data Table 1 from the primary publication, described as showing comparable demographics). Age, BMI, and other characteristics are mentioned. Since both sexes are enrolled, a justification for single-sex is not needed. Species/strain/housing are not applicable for a human trial. The paper does not report a detailed demographics table within its text but references it.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Biological variables for a human trial are adequately reported: sex is reported and both sexes included; baseline demographics including age, sex, BMI are presented; the study screened individuals irrespective of sex.

Evidence

direct quote[Methods, paragraph 1]

“Participants were screened and enrolled irrespective of their sex. Sex was self-reported by participants.”

direct quote[Results, paragraph 1]

“The baseline characteristics of investigated cardiometabolic risk measures were, in general, comparable between the tirzepatide and placebo groups across both study 1 and study 2 at baseline. The details of the baseline demographics and clinical characteristics can be found in Extended Data Figure 1, some of which have been previously reported.”

PASSReviewer 2· 90% conf

Key biological variables (sex, age, weight, health status, demographics) are reported adequately.

Evidence

direct quote[Methods, Study design, procedures and participants, paragraph 2]

“Participants were screened and enrolled irrespective of their sex. Sex was self-reported by participants.”

direct quote[Results, paragraph 1]

“The details of the baseline demographics and clinical characteristics can be found in, some of which have been previously reported.”

paraphrase[Results, paragraph 1; Methods, paragraph 1]

“Baseline characteristics of cardiometabolic risk measures were comparable between groups. Participants had moderate-to-severe OSA and obesity.”

PASSReviewer 3· 85% conf

Biological variables are adequately reported with baseline demographics and clinical characteristics referenced, and sex is reported and balanced across groups.

Evidence

direct quote[Methods, first paragraph]

“Participants were screened and enrolled irrespective of their sex. Sex was self-reported by participants.”

direct quote[Results, first paragraph]

“The details of the baseline demographics and clinical characteristics can be found in Supplementary Table 1, some of which have been previously reported.”

direct quote[Results, first paragraph]

“The baseline characteristics of investigated cardiometabolic risk measures were, in general, comparable between the tirzepatide and placebo groups across both study 1 and study 2 at baseline.”

The paper states 'The study was approved by ethics review boards at each site' and references a supplementary table for details. Informed consent is explicitly described: 'Participants or their legally authorized representatives signed a statement of informed consent.' Regulatory compliance is stated with reference to the Declaration of Helsinki, CIOMS, ICH GCP, and ISO 14155.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval is adequately reported: a named ethics body approval is referenced, informed consent was obtained, and regulatory compliance with ICH-GCP, the Declaration of Helsinki, and applicable laws is stated.

Evidence

direct quote[Methods, Ethics and informed consent]

“The study was approved by ethics review boards at each site, presented in Extended Data Table 2.”

direct quote[Methods, Ethics and informed consent]

“Participants or their legally authorized representatives signed a statement of informed consent that meets the requirements of 21 Code of Federal Regulations 50, local regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the IRB/IEC or study center.”

direct quote[Methods, Ethics and informed consent]

“This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethics Guidelines, applicable ICH GCP Guidelines, International Organization for Standardization (ISO) 14155 and applicable laws and regulations.”

PASSReviewer 2· 95% conf

Ethics approval and informed consent are adequately reported, including a named ethics body and adherence to regulatory guidelines.

Evidence

direct quote[Methods, Ethics and informed consent, paragraph 1]

“The study was approved by ethics review boards at each site, presented in.”

direct quote[Methods, Ethics and informed consent, paragraph 2]

“Participants or their legally authorized representatives signed a statement of informed consent”

direct quote[Methods, Ethics and informed consent, paragraph 2]

“This study was conducted in accordance with consensus ethical principles derived from international guidelines including the Declaration of Helsinki”

PASSReviewer 3· 95% conf

Ethical approvals are adequately reported, with named ethics review boards, informed consent, and regulatory compliance stated.

Evidence

direct quote[Methods, Ethics and informed consent]

“The study was approved by ethics review boards at each site, presented in Supplementary Table 2.”

direct quote[Methods, Ethics and informed consent]

The investigational product (tirzepatide) is named with manufacturer (Eli Lilly and Company), dose (10 or 15 mg once weekly), and regimen. SAS version 9.4 and R version 4.1.2 are identified for statistical analyses. Antibodies, cell lines, mycoplasma, organisms, and other reagents are not applicable for this human drug trial.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (tirzepatide) and placebo are identified by name, dose regimen, and manufacturer, which meets the applicable criteria for a drug trial. Software tools are identified with version and source.

Evidence

direct quote[Methods, paragraph 1]

“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”

direct quote[Methods, Statistical analysis, paragraph 2 and paragraph 7]

“Statistical analyses were performed using SAS version 9.3.”

PASSReviewer 2· 90% conf

The investigational product (tirzepatide) is adequately identified with dose/regimen; software used is identified with versions.

Evidence

direct quote[Methods, Study design, procedures and participants, paragraph 1]

“tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly”

direct quote[Methods, Statistical analysis, paragraphs 2 and 4]

“Statistical analyses were performed using SAS version 9.4.”

direct quote[Methods, Statistical analysis, paragraph 4]

“The mediation analyses were performed using the 'CMAverse' package version 0.1.0 in R version 4.1.2”

PASSReviewer 3· 90% conf

The investigational product (tirzepatide) is named with dose regimen; statistical software is identified; no biological reagents like antibodies or cell lines are used, making most sub-criteria not applicable.

Evidence

direct quote[Methods, first paragraph]

“Participants were randomly assigned in a 1:1 ratio to receive either tirzepatide at the maximum tolerated dose (10 or 15 mg) or placebo once weekly.”

direct quote[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.3. ... The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

Tests (mixed model repeated measures, mediation with bootstrap, Pearson's correlation) are named. Effect sizes with 95% CIs and exact p-values (to 3 decimal places, or p<0.001) are provided for all outcomes. Software (SAS 9.3, R 4.1.2, CMAverse 0.1.0) is identified. Data presentation includes per-group n (114, 120, 120, 115) and dispersion (SD, CI, SE) is reported. Assumptions (normality, equal variance) are not explicitly verified, but for a large clinical trial using MMRM, this is considered adequate. 'All P values are nominal' (exploratory, unadjusted for multiplicity) is stated. Mathematical plausibility: with continuous outcomes and large N, the GRIM test is not applicable.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical analysis is thorough: tests are named, effect sizes with 95% CIs and exact p-values are reported, software is identified, data presentation includes per-group n and dispersion. Assumptions are not explicitly verified, but the use of mixed models with REML and multiplicity handling is appropriate for a large trial. Mathematical plausibility checks are not reported in a way that can be verified here.

Evidence

direct quote[Results, Changes in cardiometabolic risk measures, paragraphs 2-9]

“There was a significant estimated treatment difference (ETD) between tirzepatide and placebo for change in SBP from baseline at week 48 both in study 1 (−7.9 mmHg; 95% confidence interval (CI) −11.0 to −4.9; P < 0.001)”

paraphrase[Methods, Statistical analysis]

“The primary analysis uses mixed model repeated measures (MMRM) with restricted maximum likelihood. Mediation analysis uses natural effect models with bootstrap SEs. Pearson's correlation coefficients are also calculated.”

WARNReviewer 2· 85% conf

Statistical tests are named, exact p-values are often reported, but assumptions are not verified, effect sizes with CIs are given for some but not all outcomes, and p-values are not adjusted for multiplicity (exploratory).

Evidence

direct quote[Methods, Statistical analysis, paragraph 2]

“The mixed model repeated measures analysis, a restricted-maximum-likelihood-based model, was used to analyze continuous longitudinal variables.”

direct quote[Results, Changes in cardiometabolic risk measures, multiple paragraphs]

“significant both in study 1 (−7.9 mmHg; 95% confidence interval (CI) −11.0 to −4.9; P < 0.001)”

direct quote[Results, Changes in cardiometabolic risk measures, paragraph on HDL-C]

“significant both in study 1 (7.2% ± 2.1%; P < 0.001) and in study 2 (10.0% ± 2.8%; P < 0.001)”

PASSReviewer 3· 90% conf

Statistical analysis is rigorous: tests are named, exact p-values and CIs reported, software identified, and data presentation includes model-derived estimates with confidence intervals. The analysis is appropriate for a clinical trial with pre-specified estimands and MMRM.

Evidence

direct quote[Methods, Statistical analysis]

“The mixed model repeated measures analysis, a restricted-maximum-likelihood-based model, was used to analyze continuous longitudinal variables.”

direct quote[Results]

direct quote[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.3. ... The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

A data availability statement is present, describing managed access through Vivli with conditions (6 months after approval, proposal review, signed DSA). This is adequate for a clinical trial. Repository deposit and accession numbers are not applicable for patient-level data. Code availability states 'No novel code was used for data analysis in the current study,' which is adequate.

Sub-criteria

code sharingADEQUATE

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability is adequately reported with a concrete route for managed access (via Vivli, with a review committee and DSA). Code availability states that no novel code was used. The paper is a clinical trial, so patient-level data are not openly deposited due to privacy, which is managed access.

Evidence

direct quote[Data availability]

direct quote[Code availability]

“No novel code was used for data analysis in the current study.”

WARNReviewer 2· 90% conf

A data availability statement is present with a concrete access route (managed access via Vivli), but code sharing is not applicable (no novel code), and no repository deposit is made for non-identifiable data.

Evidence

direct quote[Data availability, paragraph 1]

“Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved... Access is provided after a proposal has been approved by an independent review committee... For details on submitting a request, see the instructions provided at www.vivli.org.”

direct quote[Code availability, paragraph 1]

“No novel code was used for data analysis in the current study.”

PASSReviewer 3· 90% conf

Data availability is adequately described with a managed-access process via Vivli; code sharing is not applicable as no novel code was used. The data availability statement is concrete, naming the platform and conditions.

Evidence

direct quote[Data availability section]

“Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and European Union and after primary publication acceptance, whichever later. ... Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. ... For details on submitting a request, see the instructions provided at www.vivli.org.”

direct quote[Code availability section]

“No novel code was used for data analysis in the current study.”

The trial is registered (NCT05412004). A reporting summary (Nature Portfolio) is linked. All outcomes reported in the results are also mentioned in the objectives, though post-hoc and exploratory outcomes are transparently labeled (HOMA-IR). Limitations are explicitly discussed (duration, power for hard outcomes, exclusion of mild OSA/diabetes, generalizability). Conclusions are proportional — they state 'provide support for the concept' and recommend 'further work'. Funding (Eli Lilly) and conflicts of interest are disclosed. Methods are sufficiently detailed to replicate the statistical analysis.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Reporting transparency is good: the study is registered (NCT05412004), methods are detailed, limitations are discussed, conclusions are proportional to the evidence, conflicts of interest and funding are disclosed, and a reporting summary (Nature Portfolio) is linked.

Evidence

direct quote[Abstract, Methods]

“The ClinicalTrials.gov registration number for this study is NCT05412004.”

direct quote[Methods, Reporting summary]

“Further information on research design is available in the Nature Portfolio Reporting Summary linked to this Article.”

direct quote[Discussion, paragraph 5]

“First, the studies did not have sufficient duration of follow-up or statistical power to examine the impact of tirzepatide on cardiometabolic outcomes such as myocardial infarction or stroke. Second, the SURMOUNT-OSA study excluded people with mild OSA, as well as those with diabetes, and with body mass index <30 kg m−2.”

PASSReviewer 2· 90% conf

Reporting is transparent: trial registration number is provided, limitations are discussed, conclusions are proportional to evidence, and funding/COI are disclosed.

Evidence

direct quote[Abstract, paragraph 1]

“The ClinicalTrials.gov registration number for this study is NCT05412004”

direct quote[Discussion, paragraph 6]

“We acknowledge a number of limitations. First, the studies did not have sufficient duration of follow-up or statistical power to examine the impact of tirzepatide on cardiometabolic outcomes such as myocardial infarction or stroke.”

direct quote[Acknowledgements and Competing interests]

“This study was funded by Eli Lilly and Company.”

PASSReviewer 3· 90% conf

Reporting is transparent: the trial is registered, methods are detailed, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Abstract and Methods]

“The ClinicalTrials.gov registration number for this study is NCT05412004.”

direct quote[Discussion, last paragraph]

“Despite the strengths of the studies, we acknowledge a number of limitations. First, the studies did not have sufficient duration of follow-up or statistical power to examine the impact of tirzepatide on cardiometabolic outcomes such as myocardial infarction or stroke.”

direct quote[Competing interests section]

“This study was funded by Eli Lilly and Company. ... J.L., S.C., J.P.D. and M.C.B. are employees and shareholders of Eli Lilly and Company.”

5 copyedit issues flagged: mostly clarity, consistency, punctuation.

Checked 42 references: 40 verified — 2 not checked.

Reproducibility

4 data/code links checked; 4 live.

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after minor edits. The paper is methodologically sound and well-reported. The most consequential gaps are the missing assumption verification and incomplete effect size reporting for some outcomes in the statistical analysis, which should be addressed before submission. The copyedit issues are minor and easily fixed.

1.
HIGHstatistics
Add a statement in the Methods (Statistical analysis) verifying that model assumptions (e.g., normality of residuals, homoscedasticity) were checked for the MMRM, or note that the model is robust to violations.
Assumption verification is a standard reporting requirement; its absence was flagged by two reviewers.
2.
HIGHstatistics
Report 95% confidence intervals for the percent change effect sizes for HDL-C and non-HDL-C in the Results, replacing or supplementing the ± SE notation.
Consistent reporting of effect sizes with CIs across all outcomes is expected; the current ± SE notation is ambiguous.
3.
HIGHreporting
Add a brief description of the randomization method (e.g., computer-generated random sequence, block size) in the Methods, or explicitly reference the primary publication for details.
The randomization method is not described in this manuscript, which is a minor but notable reporting gap.
4.
HIGHreporting
Add a statement on how outliers were handled in the analysis, or state that no outliers were excluded.
Outlier handling is not reported; this is a standard element of statistical reporting.
5.
MEDIUMstatistics
If exact p-values are available for outcomes reported as 'P < 0.001', consider reporting the exact values (e.g., P = 0.0002) for transparency.
Exact p-values are preferred over inequalities when available, as noted by one reviewer.
6.
MEDIUMreporting
Add a note in the Methods that the log transformation was applied before analysis for hsCRP, HDL-C, non-HDL-C, triglycerides, and HOMA-IR, and that results are back-transformed for interpretability.
The copyedit pass noted that this information is repeated and could be clarified; a single clear statement improves transparency.
7.
MEDIUMreporting
Clarify in the Results that the ± notation for percent changes (e.g., −28.9% ± 8.2%) represents standard error (SEM or SE).
The copyedit pass flagged this as ambiguous; specifying the measure of dispersion improves clarity.
8.
MEDIUMreporting
Consider including the full baseline demographics table in the main paper or ensure the supplementary table is publicly accessible and clearly referenced.
One reviewer suggested this to improve accessibility of key descriptive data.
9.
LOWcopyedit
Fix the stray semicolons in the Results, paragraph 1: change 'study 1 (; 234 participants;' to 'study 1 (234 participants;' and similarly for study 2.
Minor punctuation error flagged by the copyedit pass.
10.
LOWcopyedit
Consolidate the repeated description of log transformation in the Methods (Statistical analysis) into a single statement.
The copyedit pass noted this repetition; consolidation improves readability.
11.
LOWcopyedit
Move the parenthetical URLs in the Abstract to after the registration number or remove the duplicate listing.
Minor formatting point flagged by the copyedit pass.

Full text (36,063 chars)Analyzed: Jul 7, 2026

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