Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

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

Name: Kaimen Rigor review — 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: 90
Author: Alpha1

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

Paper source

Read full text (PMC)

Embed this Rigor badge

Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 3 high issues for “Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.”

Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

Read alongside

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

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

Read full text (PMC)

DOI

10.1038/s41591-025-04071-1

Share this Kaimen Rigor review

Post on X Share on LinkedIn Share via Email

Embed this Rigor badge

<a href="https://alpha1science.com/verify/8b4c285e-1ef3-42cc-bb0a-8cda3b637144" target="_blank" rel="noopener">
  <img src="https://alpha1science.com/verify/8b4c285e-1ef3-42cc-bb0a-8cda3b637144/badge" alt="Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 3 high issues for “Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.”" width="440" height="104" style="max-width:100%;height:auto" />
</a>

Every embed links back to this Kaimen Rigor review.

Record fingerprint

09bc78ea303f2a8881935b54a739bb2b933cddd76355864a31eb3a5d4073a804

Verify via API

Issued Aug 10, 2026Engine 7.29.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Alpha¹ by Kaimen

Fetching the latest research

Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

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

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

Paper source

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

Read full text (PMC)

Embed this Rigor badge

Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingStudy design partially met−0.25★

Model-reported confidence: highReviewer agreement: moderateEngine: 7.29.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on changes in surrogate biomarkers (hsCRP, lipids, fasting insulin, HOMA-IR) and blood pressure, not on hard clinical outcomes. The paper explicitly acknowledges the trials lacked power to assess hard outcomes like myocardial infarction or stroke. No validated evidence linking these specific surrogates to clinical outcomes is cited, and target engagement at the tested dose is not demonstrated beyond the observed biomarker changes.
“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.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The reported effects (e.g., -7.9 mmHg SBP, -28.9% to -45.1% hsCRP, -48.0% to -54.5% HOMA-IR) are statistically significant, but the paper merely asserts they are 'clinically meaningful' without providing any minimal clinically important difference (MCID) or anchor to established thresholds. No objective criterion is given to support the clinical meaningfulness claim.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful”
Find in source

Findings by category

01ArithmeticNone found 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit4 minor suggestions

This Kaimen Rigor review uses Kaimen 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 of two well-conducted randomized trials, with generally rigorous methods and transparent reporting. However, several reporting gaps are present: the randomization method and power analysis are not described, inclusion/exclusion criteria are only referenced, p-values are often reported as thresholds, and the ethics board is not named in the main text. These are fixable reporting issues rather than fundamental methodological flaws, but they reduce the paper's standalone completeness.

This assessment is based on three independent reviews of the same paper, with the copyedit pass and verification components (citation, statistics, reproducibility, preregistration, claim audit) integrated. The reviewers diverged on study design (pass vs. warn), ethical approvals (pass vs. warn), and statistical analysis (pass vs. warn); the synthesized judgments reflect the preponderance of evidence. The statistics verification covered only 5 recomputable tests; all were consistent, but most p-values could not be independently verified. No retracted or unfound references were identified.

Numerical inconsistencies

None found

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Checked — nothing surfaced.

Recomputed 5 tests: 5 consistent, 0 inconsistent; 5 via agent-written checks.

Overstated conclusions

3 findings · worst high

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

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

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Study-design details incomplete (controls, blinding, power)Assessed

Eight Dimensions7 pass · 1 warn

The introduction cites relevant literature on OSA-related cardiovascular risk, the limitations of PAP therapy, the role of obesity, and the effects of tirzepatide on weight and glucose control. It then formulates a clear hypothesis and addresses limitations of prior research such as the lack of consistent cardiovascular benefits with PAP. All three sub-criteria are adequately reported.

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 by citing prior work on OSA, obesity, PAP therapy, and tirzepatide, and provides a logical rationale for the hypothesis that tirzepatide improves cardiometabolic risk.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“Obstructive sleep apnea (OSA) is a common disorder with major cardiometabolic and neurocognitive sequelae. Excess adiposity is a major reversible etiologic risk factor for OSA and its complications. Nasal continuous positive airway pressure (PAP) to this point has been first line therapy for OSA but is not always well tolerated. Moreover, PAP has not shown consistent benefits in patients with OSA from the perspective of cardiovascular outcomes.”

“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.”

Introduction ¶5Find in source

paraphrase[Discussion, paragraphs 2-3]

“The paper discusses that randomized trials have not demonstrated significant effect of PAP therapy on major cardiovascular outcomes and proposes potential explanations, including adherence issues and the need to address obesity.”

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Introduction, paragraphs 1-3]

“Obstructive sleep apnea (OSA) is a common disorder with major cardiometabolic and neurocognitive sequelae... Nasal continuous positive airway pressure (PAP) to this point has been first line therapy for OSA but is not always well tolerated... Considerable interest has been accumulated regarding the use of tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, which has previously been shown to improve body weight as well as glucose control.”

“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.”

Introduction ¶4Find in source

“randomized trials so far have not demonstrated significant effect of PAP therapy on major cardiovascular outcomes”

Discussion ¶3Find in source

PASSReviewer 3· 90% conf

The paper establishes a clear scientific foundation: OSA-obesity-cardiometabolic links, the limitations of PAP therapy, and the gap regarding whether tirzepatide benefits derive from weight loss or OSA improvement.

Evidence

paraphrase[Introduction]

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

IntroductionFind in source

“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.”

IntroductionFind in source

The paper states that participants were randomly assigned in a 1:1 ratio but does not specify the method (e.g., computer-generated random numbers). No a priori power or sample size calculation is provided. Inclusion/exclusion criteria are referenced to a previous publication, and the handling of missing data is described. Blinding is adequately reported. Overall, 3 of 6 applicable sub-criteria are adequate.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionINADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

The study is based on a randomized double-blind placebo-controlled design, but the randomization method is not described and no power analysis is reported for these secondary outcomes, leading to a warn.

Evidence

“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.”

MethodsFind in source

absence[Methods, Statistical analysis; Discussion, Limitations]

No power analysis is reported for the outcomes analyzed.

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

AbstractFind in source

PASSReviewer 2· 85% conf

The study design is generally rigorous, with randomization, blinding, and pre-specified inclusion/exclusion criteria, though the randomization method is not detailed and an a priori power analysis is not reported.

Evidence

“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.”

MethodsFind in source

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

AbstractFind in source

paraphrase[Methods, Study design, procedures and participants and Discussion]

“the SURMOUNT-OSA study excluded people with mild OSA, as well as those with diabetes, and with body mass index <30 kg m−2”

WARNReviewer 3· 70% conf

The trial is randomized, double-blind and placebo-controlled with multiple imputation and imputation-of-missing-data handling, but this secondary-analysis paper does not state the randomization method, a priori power analysis, or full eligibility criteria (referenced to prior publication).

Evidence

“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.”

MethodsFind in source

“the two studies’ full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously”

MethodsFind in source

“missing values were imputed using multiple imputation based on the reason of intercurrent events.”

Statistical analysisFind in source

“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.”

DiscussionFind in source

The paper provides a comprehensive baseline table (Table 1) with demographics (age, sex, BMI, OSA severity, hypertension, prediabetes, etc.). Both sexes are enrolled, and the proportion is reported. Sex-justified is not applicable as both sexes are included. Age, weight (BMI), and health status are reported. Species/strain and housing conditions are not applicable for a human study.

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

Sex, age, weight (BMI), and health status are reported in the baseline table, but race/ethnicity is not reported, making demographics sub-criterion inadequate.

Evidence

paraphrase[Table 1]

“Age, years: 47.3±11.0 (tirzepatide study 1); Female, n (%): 36 (31.6) (tirzepatide study 1)”

paraphrase[Table 1]

“Hypertension, n (%): 84 (73.7) (tirzepatide study 1); Prediabetes, n (%): 74 (64.9) (tirzepatide study 1)”

absence[Table 1 and Methods]

Race/ethnicity is not reported.

PASSReviewer 2· 95% conf

Biological variables and subject characteristics are well reported, including age, sex, BMI, health status, and comorbidities.

Evidence

paraphrase[Results, Table 1]

“Table 1 | Baseline demographics and clinical characteristics ... Age, years ... Female, n (%) ... BMI, kgm−2 ... Hypertension, n (%) ... Prediabetes, n (%)”

paraphrase[Results, Table 1]

“Female, n (%) ... 36 (31.6) ... 41 (34.2) ... 33 (27.5) ... 32 (27.8)”

PASSReviewer 3· 85% conf

Sex, age, BMI, HbA1c, comorbidities and other clinical characteristics are reported in baseline Table 1; both sexes were enrolled so no single-sex justification is required.

Evidence

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

Table 1Find in source

“Age, years | 47.3±11.0 | 48.4±11.9 | 47.9±11.5”

Table 1Find in source

The paper states that the study was approved by ethics review boards at each site (referenced to supplementary), that participants or their representatives signed informed consent, and that the study was conducted in accordance with the Declaration of Helsinki and other applicable guidelines. All three applicable sub-criteria are reported and adequate.

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 review board approval, informed consent, and regulatory compliance are all adequately reported.

Evidence

paraphrase[Methods, Ethics and informed consent]

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

“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.”

MethodsFind in source

“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.”

MethodsFind in source

WARNReviewer 2· 90% conf

Ethical approval is mentioned but the approving body is not named, and the protocol number is not provided; informed consent and regulatory compliance are adequately reported.

Evidence

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

MethodsFind in source

PASSReviewer 3· 85% conf

Ethics approval by review boards at each site, signed informed consent, and compliance with the Declaration of Helsinki, ICH GCP and ISO 14155 are all stated.

Evidence

paraphrase[Methods, Ethics and informed consent]

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

“Participants or their legally authorized representatives signed a statement of informed consent that meets the requirements of 21 Code of Federal Regulations 50”

MethodsFind in source

The drug name, dose, and manufacturer (Eli Lilly) are provided. Statistical software (SAS version 9.3, R version 4.1.2, package 'CMAverse' version 0.1.0) is identified. No antibodies, cell lines, or experimental animals are used, so those sub-criteria are not applicable.

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· 90% conf

The investigational product is identified with dose and regimen, and statistical software is specified with versions. Other resource types are not applicable.

Evidence

“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.”

MethodsFind in source

paraphrase[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.4. The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

PASSReviewer 2· 95% conf

The investigational drug (tirzepatide) and statistical software are adequately identified; no other biological resources are applicable.

Evidence

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

MethodsFind in source

paraphrase[Methods, Statistical analysis]

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

PASSReviewer 3· 85% conf

The investigational product (tirzepatide, dose/regimen) and all analysis software (SAS 9.3, R 4.1.2, CMAverse 0.1.0) are identified; bench-resource criteria are not applicable.

Evidence

paraphrase[Methods, Study design]

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

“Statistical analyses were performed using SAS version 9.3.”

Statistical analysisFind in source

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

Statistical analysisFind in source

The paper specifies mixed model repeated measures and mediation analysis with natural effect models. All estimates are reported with 95% CIs and exact p-values (e.g., P < 0.001, P = 0.007). SAS and R versions are given. Data presentation includes LS means ± SE and per-group n. Assumptions are not explicitly tested but are handled by the pre-specified analysis model. Mathematical plausibility is not applicable due to continuous outcomes and large N. All applicable sub-criteria are adequate.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical tests are named, effect sizes with 95% CIs are reported, software is identified, and data presentation is adequate for a clinical trial. Assumptions are handled by design, and exact p-values are provided.

Evidence

paraphrase[Methods, Statistical analysis]

“The mixed model repeated measures analysis, a restricted-maximum-likelihood-based model, was used to analyze continuous longitudinal variables. Mediation analyses were conducted to decompose the total effect of tirzepatide on cardiometabolic risk markers into direct effect and indirect effect.”

“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) and in study 2 (−4.3 mmHg; 95% CI −7.3 to −1.2; P = 0.007).”

ResultsFind in source

paraphrase[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.4. The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

PASSReviewer 2· 85% conf

Statistical methods are generally appropriate and well-described, though some p-values are reported as thresholds rather than exact values.

Evidence

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

Statistical analysisFind in source

paraphrase[Results, Table 2]

“Change in SBP (mmHg) from baseline at week 48 ... −7.9 (−11.0 to −4.9) ... −4.3 (−7.3 to −1.2)”

paraphrase[Results, Table 2]

“P < 0.001”

WARNReviewer 3· 65% conf

Statistical tests (MMRM, bootstrap-mediated natural-effect models, Pearson correlation), software, effect sizes with CIs and per-group n are well reported; however many p-values are printed only as 'P < 0.001' thresholds, which is imprecise reporting.

Evidence

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

Statistical analysisFind in source

“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)”

ResultsFind in source

paraphrase[Results; Table 2]

“P < 0.001”

“Statistical analyses were performed using SAS version 9.3.”

Statistical analysisFind in source

The paper includes a detailed data availability statement describing that individual participant data are available after anonymization through a proposal process managed by a review committee via Vivli. Source data are provided with the paper. No custom code was used; all analyses were performed with standard software packages. All applicable sub-criteria are adequate.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The data availability statement provides a concrete access route via the Vivli platform, and no custom code was used, so code sharing is not applicable.

Evidence

paraphrase[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 is later. No expiration date of data requests is currently set once data are made available. 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. Data and documents, including the clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.”

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

Data availabilityFind in source

PASSReviewer 2· 95% conf

A detailed data availability statement is provided, specifying access through a managed platform (Vivli) with conditions; no novel code was used, so code sharing is not applicable.

Evidence

Data availabilityFind in source

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

Data availabilityFind in source

PASSReviewer 3· 90% conf

A concrete data-access route is provided via the Vivli platform with stated conditions and timeframe; repository/accession are not applicable for identifiable patient data, and no novel code was used.

Evidence

“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.”

Data availabilityFind in source

“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 is later.”

Data availabilityFind in source

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

Data availabilityFind in source

The trial is registered at ClinicalTrials.gov (NCT05412004). The Nature Portfolio Reporting Summary is linked. All prespecified and post hoc outcomes are reported, including non-significant results. Limitations are discussed in a dedicated paragraph. Conclusions are proportional to the evidence. Funding and competing interests are fully disclosed. All applicable sub-criteria are adequate.

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· 95% conf

The paper is well-reported with trial registration, reference to a reporting guideline, comprehensive outcome reporting, limitations discussion, proportional conclusions, and funding/COI statements.

Evidence

paraphrase[Abstract, Methods]

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

“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.”

Discussion ¶5Find in source

paraphrase[Acknowledgements and Competing interests sections]

“This study was funded by Eli Lilly and Company. The study sponsor had a role in the study design, data collection, data analysis, interpretation of data, writing of the report and the decision to submit the paper for publication. Competing interests: [detailed list]”

PASSReviewer 2· 95% conf

The reporting is transparent: methods are detailed, trial registration is provided, limitations are discussed, and conclusions are proportional to the evidence.

Evidence

“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”

AbstractFind in source

Discussion ¶7Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was funded by Eli Lilly and Company. ... Competing interests ... A.M. reports income from Eli Lilly, Livanova, Zoll and Powell Mansfield.”

PASSReviewer 3· 85% conf

Methods are detailed, the trial is registered (NCT05412004), a Nature Portfolio Reporting Summary is linked, limitations are extensively discussed, conclusions are hedged appropriately, and funding/COI are disclosed.

Evidence

“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”

AbstractFind in source

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

AbstractFind in source

“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.”

DiscussionFind in source

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

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 42 references by DOI: 40 verified — 2 no DOI (shown, not verified).

3 data/code links checked; 3 live.

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly consistency, clarity, typo.

Kaimen Rigor Action ItemsFinal pass before journal submission

This is a post-publication robustness assessment. The published work is generally robust, but an informed reader should note the following gaps that reduce methodological transparency: the randomization method is not described, no power analysis is provided for the secondary outcomes, inclusion/exclusion criteria are not fully restated, p-values are partially reported as thresholds, and the ethics board is not named in the main text. These issues do not invalidate the conclusions but would warrant a correction or erratum to address the most critical gaps (randomization method, power analysis, ethics board name). An independent re-analysis would benefit from the detailed data availability statement.

1.
HIGHreporting
In the Methods section (Study design, procedures and participants), specify the randomization method (e.g., computer-generated random numbers, block size, stratification factors) to meet the randomization_method sub-criterion.
The current statement 'randomly assigned in a 1:1 ratio' is insufficient for replication assessment; the method is a standard reporting requirement for RCTs.
2.
HIGHreporting
In the Methods (Statistical analysis) or Discussion (Limitations), include a clear statement about the lack of a priori power analysis for these secondary outcomes, or reference the primary study's power calculation and note that these analyses are exploratory.
The absence of a power analysis for the reported outcomes reduces the reader's ability to interpret the statistical precision of the estimates.
3.
HIGHreporting
In the Methods (Ethics and informed consent), name the specific ethics review board(s) that approved the study and provide the protocol approval number, rather than only referencing supplementary material.
A clear ethics approval statement in the main text is a standard reporting requirement and improves transparency.
4.
MEDIUMreporting
In the Methods (Study design, procedures and participants), restate the full key inclusion and exclusion criteria rather than solely referencing the prior publication.
The paper should be self-contained for readers who do not have access to the primary publication, and the criteria are essential for understanding the study population.
5.
MEDIUMstatistics
In the Results (Table 2 and text), replace threshold p-values (e.g., 'P < 0.001') with exact p-values (e.g., 'P = 0.0003') where the software output provides them, to improve precision.
Exact p-values allow readers to assess the strength of evidence more precisely than threshold reporting.
6.
MEDIUMreporting
In the baseline table (Table 1), add race/ethnicity data to complete the demographic reporting.
Race/ethnicity is a standard demographic variable in human studies and its absence limits the generalizability assessment.
7.
LOWreporting
In the Methods (Statistical analysis), clarify the SAS version used (9.3 vs. 9.4) to resolve the discrepancy between reviewers.
Inconsistent reporting of software version could confuse readers attempting to replicate the analyses.
8.
LOWcopyedit
In the Competing interests section, correct the typo 'USCD' to 'UCSD' (University of California San Diego).
This is a factual error in an institutional abbreviation that should be corrected.
9.
LOWcopyedit
In the Abstract, remove the article 'a' in 'changes in a homeostatic model assessment for insulin resistance' to read 'changes in homeostatic model assessment for insulin resistance'.
Grammatical correction for clarity.
10.
LOWcopyedit
In the Methods (Statistical analysis), hyphenate 'post-baseline' consistently (change 'postbaseline' to 'post-baseline' or vice versa).
Consistent hyphenation improves readability.
11.
LOWcopyedit
In Table 1 footnote, use 'mean ± s.d.' with spaces around the plus-minus sign for consistency.
Consistent formatting improves readability.

Full text (39,175 chars)Analyzed: Aug 10, 2026

Start the discussion on JRNLClub

Community discussion on jrnlclub.com

Read alongside

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

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

Read full text (PMC)

DOI

10.1038/s41591-025-04071-1

Share this Kaimen Rigor review

Post on X Share on LinkedIn Share via Email

Embed this Rigor badge

<a href="https://alpha1science.com/verify/8b4c285e-1ef3-42cc-bb0a-8cda3b637144" target="_blank" rel="noopener">
  <img src="https://alpha1science.com/verify/8b4c285e-1ef3-42cc-bb0a-8cda3b637144/badge" alt="Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 3 high issues for “Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.”" width="440" height="104" style="max-width:100%;height:auto" />
</a>

Every embed links back to this Kaimen Rigor review.

Record fingerprint

09bc78ea303f2a8881935b54a739bb2b933cddd76355864a31eb3a5d4073a804

Verify via API

Issued Aug 10, 2026Engine 7.29.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingStudy design partially met−0.25★

Model-reported confidence: highReviewer agreement: moderateEngine: 7.29.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on changes in surrogate biomarkers (hsCRP, lipids, fasting insulin, HOMA-IR) and blood pressure, not on hard clinical outcomes. The paper explicitly acknowledges the trials lacked power to assess hard outcomes like myocardial infarction or stroke. No validated evidence linking these specific surrogates to clinical outcomes is cited, and target engagement at the tested dose is not demonstrated beyond the observed biomarker changes.
“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.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The reported effects (e.g., -7.9 mmHg SBP, -28.9% to -45.1% hsCRP, -48.0% to -54.5% HOMA-IR) are statistically significant, but the paper merely asserts they are 'clinically meaningful' without providing any minimal clinically important difference (MCID) or anchor to established thresholds. No objective criterion is given to support the clinical meaningfulness claim.
“The improvements in cardiometabolic risk measures were both statistically significant and clinically meaningful”
Find in source

Findings by category

01ArithmeticNone found 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit4 minor suggestions

Numerical inconsistencies

None found

Checked — nothing surfaced.

Recomputed 5 tests: 5 consistent, 0 inconsistent; 5 via agent-written checks.

Overstated conclusions

3 findings · worst high

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

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

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Study-design details incomplete (controls, blinding, power)Assessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Evidence

paraphrase[Introduction, paragraphs 1-3]

Introduction ¶5Find in source

paraphrase[Discussion, paragraphs 2-3]

PASSReviewer 2· 95% conf

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

Evidence

paraphrase[Introduction, paragraphs 1-3]

“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.”

Introduction ¶4Find in source

“randomized trials so far have not demonstrated significant effect of PAP therapy on major cardiovascular outcomes”

Discussion ¶3Find in source

PASSReviewer 3· 90% conf

Evidence

paraphrase[Introduction]

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

IntroductionFind in source

“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.”

IntroductionFind in source

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionINADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Evidence

“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.”

MethodsFind in source

absence[Methods, Statistical analysis; Discussion, Limitations]

No power analysis is reported for the outcomes analyzed.

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

AbstractFind in source

PASSReviewer 2· 85% conf

Evidence

“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.”

MethodsFind in source

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

AbstractFind in source

paraphrase[Methods, Study design, procedures and participants and Discussion]

“the SURMOUNT-OSA study excluded people with mild OSA, as well as those with diabetes, and with body mass index <30 kg m−2”

WARNReviewer 3· 70% conf

Evidence

“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.”

MethodsFind in source

“the two studies’ full design, key eligibility criteria, procedures and primary efficacy and safety results have been published previously”

MethodsFind in source

“missing values were imputed using multiple imputation based on the reason of intercurrent events.”

Statistical analysisFind in source

“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.”

DiscussionFind in source

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

Sex, age, weight (BMI), and health status are reported in the baseline table, but race/ethnicity is not reported, making demographics sub-criterion inadequate.

Evidence

paraphrase[Table 1]

“Age, years: 47.3±11.0 (tirzepatide study 1); Female, n (%): 36 (31.6) (tirzepatide study 1)”

paraphrase[Table 1]

“Hypertension, n (%): 84 (73.7) (tirzepatide study 1); Prediabetes, n (%): 74 (64.9) (tirzepatide study 1)”

absence[Table 1 and Methods]

Race/ethnicity is not reported.

PASSReviewer 2· 95% conf

Biological variables and subject characteristics are well reported, including age, sex, BMI, health status, and comorbidities.

Evidence

paraphrase[Results, Table 1]

“Table 1 | Baseline demographics and clinical characteristics ... Age, years ... Female, n (%) ... BMI, kgm−2 ... Hypertension, n (%) ... Prediabetes, n (%)”

paraphrase[Results, Table 1]

“Female, n (%) ... 36 (31.6) ... 41 (34.2) ... 33 (27.5) ... 32 (27.8)”

PASSReviewer 3· 85% conf

Sex, age, BMI, HbA1c, comorbidities and other clinical characteristics are reported in baseline Table 1; both sexes were enrolled so no single-sex justification is required.

Evidence

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

Table 1Find in source

“Age, years | 47.3±11.0 | 48.4±11.9 | 47.9±11.5”

Table 1Find in source

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 review board approval, informed consent, and regulatory compliance are all adequately reported.

Evidence

paraphrase[Methods, Ethics and informed consent]

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

MethodsFind in source

WARNReviewer 2· 90% conf

Ethical approval is mentioned but the approving body is not named, and the protocol number is not provided; informed consent and regulatory compliance are adequately reported.

Evidence

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

MethodsFind in source

PASSReviewer 3· 85% conf

Ethics approval by review boards at each site, signed informed consent, and compliance with the Declaration of Helsinki, ICH GCP and ISO 14155 are all stated.

Evidence

paraphrase[Methods, Ethics and informed consent]

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

“Participants or their legally authorized representatives signed a statement of informed consent that meets the requirements of 21 Code of Federal Regulations 50”

MethodsFind in source

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· 90% conf

The investigational product is identified with dose and regimen, and statistical software is specified with versions. Other resource types are not applicable.

Evidence

“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.”

MethodsFind in source

paraphrase[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.4. The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

PASSReviewer 2· 95% conf

The investigational drug (tirzepatide) and statistical software are adequately identified; no other biological resources are applicable.

Evidence

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

MethodsFind in source

paraphrase[Methods, Statistical analysis]

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

PASSReviewer 3· 85% conf

The investigational product (tirzepatide, dose/regimen) and all analysis software (SAS 9.3, R 4.1.2, CMAverse 0.1.0) are identified; bench-resource criteria are not applicable.

Evidence

paraphrase[Methods, Study design]

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

“Statistical analyses were performed using SAS version 9.3.”

Statistical analysisFind in source

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

Statistical analysisFind in source

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Evidence

paraphrase[Methods, Statistical analysis]

ResultsFind in source

paraphrase[Methods, Statistical analysis]

“Statistical analyses were performed using SAS version 9.4. The mediation analyses were performed using the ‘CMAverse’ package version 0.1.0 in R version 4.1.2.”

PASSReviewer 2· 85% conf

Statistical methods are generally appropriate and well-described, though some p-values are reported as thresholds rather than exact values.

Evidence

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

Statistical analysisFind in source

paraphrase[Results, Table 2]

“Change in SBP (mmHg) from baseline at week 48 ... −7.9 (−11.0 to −4.9) ... −4.3 (−7.3 to −1.2)”

paraphrase[Results, Table 2]

“P < 0.001”

WARNReviewer 3· 65% conf

Evidence

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

Statistical analysisFind in source

“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)”

ResultsFind in source

paraphrase[Results; Table 2]

“P < 0.001”

“Statistical analyses were performed using SAS version 9.3.”

Statistical analysisFind in source

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The data availability statement provides a concrete access route via the Vivli platform, and no custom code was used, so code sharing is not applicable.

Evidence

paraphrase[Data availability section]

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

Data availabilityFind in source

PASSReviewer 2· 95% conf

A detailed data availability statement is provided, specifying access through a managed platform (Vivli) with conditions; no novel code was used, so code sharing is not applicable.

Evidence

Data availabilityFind in source

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

Data availabilityFind in source

PASSReviewer 3· 90% conf

Evidence

“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.”

Data availabilityFind in source

“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 is later.”

Data availabilityFind in source

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

Data availabilityFind in source

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· 95% conf

The paper is well-reported with trial registration, reference to a reporting guideline, comprehensive outcome reporting, limitations discussion, proportional conclusions, and funding/COI statements.

Evidence

paraphrase[Abstract, Methods]

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

Discussion ¶5Find in source

paraphrase[Acknowledgements and Competing interests sections]

PASSReviewer 2· 95% conf

The reporting is transparent: methods are detailed, trial registration is provided, limitations are discussed, and conclusions are proportional to the evidence.

Evidence

“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”

AbstractFind in source

Discussion ¶7Find in source

paraphrase[Acknowledgements and Competing interests]

“This study was funded by Eli Lilly and Company. ... Competing interests ... A.M. reports income from Eli Lilly, Livanova, Zoll and Powell Mansfield.”

PASSReviewer 3· 85% conf

Evidence

“The ClinicalTrials.gov (http://ClinicalTrials.gov) registration number for this study is NCT05412004”

AbstractFind in source

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

AbstractFind in source

“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.”

DiscussionFind in source

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

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 42 references by DOI: 40 verified — 2 no DOI (shown, not verified).

3 data/code links checked; 3 live.

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly consistency, clarity, typo.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHreporting
In the Methods section (Study design, procedures and participants), specify the randomization method (e.g., computer-generated random numbers, block size, stratification factors) to meet the randomization_method sub-criterion.
The current statement 'randomly assigned in a 1:1 ratio' is insufficient for replication assessment; the method is a standard reporting requirement for RCTs.
2.
HIGHreporting
In the Methods (Statistical analysis) or Discussion (Limitations), include a clear statement about the lack of a priori power analysis for these secondary outcomes, or reference the primary study's power calculation and note that these analyses are exploratory.
The absence of a power analysis for the reported outcomes reduces the reader's ability to interpret the statistical precision of the estimates.
3.
HIGHreporting
In the Methods (Ethics and informed consent), name the specific ethics review board(s) that approved the study and provide the protocol approval number, rather than only referencing supplementary material.
A clear ethics approval statement in the main text is a standard reporting requirement and improves transparency.
4.
MEDIUMreporting
In the Methods (Study design, procedures and participants), restate the full key inclusion and exclusion criteria rather than solely referencing the prior publication.
The paper should be self-contained for readers who do not have access to the primary publication, and the criteria are essential for understanding the study population.
5.
MEDIUMstatistics
In the Results (Table 2 and text), replace threshold p-values (e.g., 'P < 0.001') with exact p-values (e.g., 'P = 0.0003') where the software output provides them, to improve precision.
Exact p-values allow readers to assess the strength of evidence more precisely than threshold reporting.
6.
MEDIUMreporting
In the baseline table (Table 1), add race/ethnicity data to complete the demographic reporting.
Race/ethnicity is a standard demographic variable in human studies and its absence limits the generalizability assessment.
7.
LOWreporting
In the Methods (Statistical analysis), clarify the SAS version used (9.3 vs. 9.4) to resolve the discrepancy between reviewers.
Inconsistent reporting of software version could confuse readers attempting to replicate the analyses.
8.
LOWcopyedit
In the Competing interests section, correct the typo 'USCD' to 'UCSD' (University of California San Diego).
This is a factual error in an institutional abbreviation that should be corrected.
9.
LOWcopyedit
In the Abstract, remove the article 'a' in 'changes in a homeostatic model assessment for insulin resistance' to read 'changes in homeostatic model assessment for insulin resistance'.
Grammatical correction for clarity.
10.
LOWcopyedit
In the Methods (Statistical analysis), hyphenate 'post-baseline' consistently (change 'postbaseline' to 'post-baseline' or vice versa).
Consistent hyphenation improves readability.
11.
LOWcopyedit
In Table 1 footnote, use 'mean ± s.d.' with spaces around the plus-minus sign for consistency.
Consistent formatting improves readability.

Full text (39,175 chars)Analyzed: Aug 10, 2026