Rigor Reviewed

Rigor-Reviewed Manuscript

Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial

Name: Adcurare Rigor Record — Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial
Item: Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial
Rating: 100
Author: Adcurare

Martin CK, Carmichael OT, Carnell S, Considine RV, Kareken DA, Dydak U, Mattes RD, Scott D, Shcherbinin S, Nishiyama H, Knights A, Urva S, Biernat L, Pratt E, Haupt A, Mintun M, Otero Svaldi D, Milicevic Z, Coskun T.

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Adcurare Rigor Review — 2★ (Weak), 0 critical, 6 high issues for “Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 4, 2026

Adcurare Rigor Review

Rigor Reviewed

2 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsStatistic did not reproduce ×2−1★
IntegrityIntegrity concern ×2−1★
CitationsCitations & links (capped) ×55−1★

Citations & links are capped at −1★ combined, however many are flagged.

Model-reported confidence: highReviewer agreement: moderateEngine: 7.4.0Source: full text

Problems surfaced3 types

Reported statistics do not recompute
Other integrity concern
References not resolvable to a published paper

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 is a well-conducted phase 1 trial with strong reporting transparency and ethical compliance. However, several methodological and reporting gaps reduce its overall robustness: the open-label comparator, lack of pre-specified outlier handling, missing assumption verification for the primary analysis, two inconsistent p-values, and absence of code sharing.

Three independent reviewers evaluated all eight dimensions; their assessments were synthesized. The statistics verification component checked 20 tests and found 2 inconsistencies. The citation check found 55 references not found in the registry (a high number, but none retracted). The reproducibility check found all 3 links live. The claim audit found no under-evidenced claims.

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

Recomputed 20 tests: 18 consistent, 2 inconsistent, 20 via agent-written checks.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction cites multiple prior studies on GLP-1 receptor agonists and tirzepatide, noting their limitations (e.g., 'did not collect brain functioning measurements'). The rationale linking tirzepatide's unknown mechanisms to the study's objectives is clearly stated, and the hypothesis follows logically. The paper explicitly addresses gaps in prior research by including both behavioral and fMRI measures. All three sub-criteria are adequately met.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study clearly establishes its scientific foundation by citing prior research on GLP-1 RAs and tirzepatide, articulating a logical rationale, and describing how limitations of prior work are addressed.

Evidence

direct quote[Introduction, paragraph 2]

“However, these studies used limited measures of ingestive behavior and did not collect brain functioning measurements that could inform CNS mechanisms.”

direct quote[Introduction, paragraph 3]

“We hypothesized that tirzepatide would decrease energy intake and appetite, and modulate activation of brain regions associated with appetite and food reward.”

direct quote[Introduction, final paragraph]

“Early adaptive changes in ingestive behavior and involvement of CNS mechanisms producing energy intake reductions with tirzepatide are yet to be fully elucidated in humans.”

PASSReviewer 2· 95% conf

The paper clearly establishes its scientific premise by citing prior research, providing a logical rationale, and addressing limitations of previous studies.

Evidence

direct quote[Introduction, paragraph 1]

“Previous studies of selective glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) using self-report inventories suggest these therapies affect ingestive behaviors”

direct quote[Introduction, last paragraph]

“We hypothesized that tirzepatide would decrease energy intake and appetite, and modulate activation of brain regions associated with appetite and food reward.”

direct quote[Introduction, paragraph 2]

“However, these studies used limited measures of ingestive behavior and did not collect brain functioning measurements that could inform CNS mechanisms.”

PASSReviewer 3· 95% conf

The scientific premise is well-established, with clear citation of prior research on GLP-1 RAs and tirzepatide, a logical rationale linking the premise to the study objectives, and an explicit description of how limitations of prior work are addressed.

Evidence

direct quote[Introduction, paragraphs 1–3]

“Previous studies of selective glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) using self-report inventories suggest these therapies affect ingestive behaviors, while functional magnetic resonance imaging (fMRI) studies using food cues show involvement of central nervous system (CNS) mechanisms.”

direct quote[Introduction, final paragraph]

“We hypothesized that tirzepatide would decrease energy intake and appetite, and modulate activation of brain regions associated with appetite and food reward.”

direct quote[Introduction, paragraph 3]

“However, these studies used limited measures of ingestive behavior and did not collect brain functioning measurements that could inform CNS mechanisms.”

Randomization is stated as 1:1:1 using a randomization table with treatment codes, stratified by BMI. Blinding is described: tirzepatide and placebo were double-blinded, liraglutide was open-label with rationale. An a priori power analysis is provided (80% power, alpha=0.05, effect size 212 kcal, SD 289 kcal). Inclusion/exclusion criteria are listed with reference to the supplement. Outlier handling is not pre-specified beyond the analysis population (all randomized participants with available data). Controls include a placebo and active comparator. Independent replication is not applicable for a single trial. Applicable sub-criteria are mostly adequate, yielding a pass.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study design is robust: randomization, blinding (partially), power analysis, and inclusion/exclusion criteria are reported. The randomization method is described in general terms but is acceptable for a clinical trial, and outlier handling is not pre-specified.

Evidence

direct quote[Methods, Randomization and masking]

“Participants were randomized 1:1:1 to receive tirzepatide, liraglutide or placebo, using a randomization table with treatment codes. Randomization was stratified by baseline BMI (27 to <30, 30 to <35 and 35 to 50 kg per m2) within each site.”

direct quote[Methods, Randomization and masking]

“The sponsor, investigators and participants were blinded to tirzepatide and placebo treatment but liraglutide treatment was open-label.”

direct quote[Methods, Statistical methods]

“This sample size provides at least 80% power for the comparison of tirzepatide versus placebo for the change in energy intake during ad libitum test meals (primary outcome) based on a two-sample t-test at an alpha level of 0.05, given an expected treatment difference of 212 kcal and an assumed common standard deviation of 289 kcal for the change in energy intake from baseline.”

PASSReviewer 2· 85% conf

The study design is adequately rigorous for a phase 1 trial, with a pre-specified power analysis, clear inclusion/exclusion criteria, and blinding for the primary comparison, though the randomization method description is somewhat vague.

Evidence

direct quote[Methods, 'Randomization and masking']

“Participants were randomized 1:1:1 to receive tirzepatide, liraglutide or placebo, using a randomization table with treatment codes.”

direct quote[Methods, 'Statistical methods']

“A total of 111 participants were planned to be randomized... This sample size provides at least 80% power for the comparison of tirzepatide versus placebo for the change in energy intake during ad libitum test meals (primary outcome) based on a two-sample t-test at an alpha level of 0.05, given an expected treatment difference of 212 kcal and an assumed common standard deviation of 289 kcal.”

direct quote[Methods, 'Randomization and masking']

“The sponsor, investigators and participants were blinded to tirzepatide and placebo treatment but liraglutide treatment was open-label.”

WARNReviewer 3· 90% conf

The study design is a randomized, partially-blinded trial with stated randomization method and unit, but has notable limitations including lack of full blinding (liraglutide open-label) and no pre-specified analysis population/missing-data plan described for the primary analysis.

Evidence

direct quote[Methods, Randomization and masking]

“Participants were randomized 1:1:1 to receive tirzepatide, liraglutide or placebo, using a randomization table with treatment codes.”

direct quote[Methods, Randomization and masking]

“The sponsor, investigators and participants were blinded to tirzepatide and placebo treatment but liraglutide treatment was open-label. Therefore, the study was considered partially blinded.”

direct quote[Methods, Statistical methods]

Sex is reported (Table 1); both females and males are enrolled, so sex_justified is not applicable. Age, weight, BMI, waist circumference, and health status (BMI 27-50, no diabetes, stable weight) are reported. Demographics (race, ethnicity) are provided. Species/strain and housing are not applicable for a human trial. All applicable sub-criteria are adequate.

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· 95% conf

Sex, age, weight/BMI, and demographics are reported in Table 1. Health status is defined by inclusion criteria. Both sexes are included, so sex justification is not applicable.

Evidence

direct quote[Table 1]

“Sex Female: 36 (92%) in placebo, 25 (66%) in liraglutide, 36 (97%) in tirzepatide. Male: 3 (8%), 13 (34%), 1 (3%).”

direct quote[Methods, Participants]

“Male and female adults (18 to 65 years) were eligible for inclusion if they had a BMI of 27 to 50 kg per m2 and stable weight in the last month (no weight change of >4 kg). Exclusion criteria included diagnosis of any form of diabetes or glycated hemoglobin ≥6.5% at screening.”

PASSReviewer 2· 95% conf

All applicable biological variables are reported in detail, including sex, age, weight/BMI, and demographics.

Evidence

direct quote[Table 1]

“Age (yr) 46.2 (9.5) ... Sex Female 36 (92%) [etc.]”

direct quote[Table 1]

“Weight (kg) 98.2 (20.8) ... BMI (kg per m2) 36.2 (5.9)”

direct quote[Table 1]

“Race White 28 (72%) ... Ethnicity Hispanic or Latino 2 (5%)”

PASSReviewer 3· 95% conf

Biological variables are well reported: sex, age, weight, BMI, race/ethnicity, and health status are tabulated. Sex is self-reported, and the imbalance is acknowledged as a limitation with a justification (reflects treatment population; not designed to test sex effects). Demographics are fully reported.

Evidence

direct quote[Table 1]

“Sex: Female 36 (92%)…Male 3 (8%)…Age (yr) 46.2 (9.5)…Weight (kg) 98.2 (20.8)…Race: White 28 (72%)…”

direct quote[Discussion, paragraph 10]

“Second, a lack of sex parity in the study, a common occurrence in obesity trials, albeit one that reflects the treatment population. … This study was not designed to test the effects of sex but future studies into the potential effects of sex on the effect of tirzepatide on energy intake and eating behaviors are warranted.”

direct quote[Results, Table 1 footnote]

“Sex was self-reported by participants.”

The methods state that the study was approved by institutional review boards at each site (Pennington Biomedical Research Center IRB, Indiana University, and Johns Hopkins IRB). All participants provided written informed consent. Regulatory compliance with the Declaration of Helsinki and ICH-GCP is explicitly affirmed.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study was approved by named IRBs at each site, written informed consent was obtained, and compliance with Declaration of Helsinki and ICH-GCP is stated.

Evidence

direct quote[Methods, Study design]

“The study was approved by institutional review boards at each site (Pennington Biomedical Research Center Institutional Review Board, Human Research Protection Program Office of Research Compliance Indiana University and Johns Hopkins Institutional Review Board).”

direct quote[Methods, Study design]

“All participants provided written informed consent before participating in the study.”

direct quote[Methods, Study design]

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines.”

PASSReviewer 2· 95% conf

Ethical approvals, informed consent, and regulatory compliance are all clearly documented.

Evidence

direct quote[Methods, 'Study design']

“All participants provided written informed consent before participating in the study.”

direct quote[Methods, 'Study design']

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines.”

PASSReviewer 3· 95% conf

Ethical approvals are adequately documented: named IRBs at each site approved the study, written informed consent was obtained, and compliance with the Declaration of Helsinki and ICH-GCP is stated. The trial is registered.

Evidence

direct quote[Methods, Study design]

“All participants provided written informed consent before participating in the study.”

direct quote[Methods, Study design]

“The study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines.”

Tirzepatide and liraglutide are described with their dosing and titration schedules. The sponsor (Eli Lilly) is the manufacturer. SAS Enterprise Guide v.8 and SPM12 are identified for statistical and fMRI analysis. Other resource types (antibodies, cell lines, etc.) are not applicable. Thus both applicable criteria are adequate.

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

WARNReviewer 1· 85% conf

The investigational drugs (tirzepatide, liraglutide) are named with doses but their manufacturer/source is not explicitly stated. Statistical software is identified. Other resource types are not applicable.

Evidence

direct quote[Methods, Procedures]

“Tirzepatide was administered at 5 mg for the first 3 weeks followed by 10 mg for the next 3 weeks. Liraglutide was self-administered once-daily by participants at home for 38 days.”

direct quote[Methods, Statistical methods]

“Analyses were carried out using SAS Enterprise Guide v.8.”

PASSReviewer 2· 90% conf

The investigational products (tirzepatide, liraglutide, placebo) are adequately identified with dosing regimens, and key software tools are named.

Evidence

direct quote[Methods, 'Procedures']

“Tirzepatide was administered at 5 mg for the first 3 weeks followed by 10 mg for the next 3 weeks.”

direct quote[Methods, 'Procedures']

“Liraglutide was initiated at 0.6 mg and escalated weekly by 0.6 mg until a dose of 3 mg was reached at week 5 and maintained for the remainder of the study.”

direct quote[Methods, 'Statistical methods']

“Analyses were carried out using SAS Enterprise Guide v.8, unless stated otherwise.”

PASSReviewer 3· 90% conf

The investigational products (tirzepatide, liraglutide, placebo) are identified with manufacturer (Eli Lilly and Company) and dosing regimens. Software tools (SAS Enterprise Guide v.8, SPM12) are identified with versions. Other reagents are not applicable.

Evidence

direct quote[Methods, Procedures]

“Tirzepatide and placebo were administered subcutaneously once-weekly at the study centers. Tirzepatide was administered at 5 mg for the first 3 weeks followed by 10 mg for the next 3 weeks.”

direct quote[Methods, Statistical methods]

“Analyses were carried out using SAS Enterprise Guide v.8, unless stated otherwise.”

direct quote[Methods, fMRI processing]

“Preprocessing of fMRI data in Statistical Parametric Mapping 12 (SPM12)”

Tests include ANCOVA, MMRM, two-sample t-test. Exact p-values are given (many <0.0001, which is acceptable for very small values). Effect sizes and 95% CIs are reported for all comparisons. Statistical software is identified (SAS v.8, SPM12). Data presentation includes LS means, SEs, CIs, and forest plots; per-group Ns are provided. Mathematical checks (statistics_checks) did not identify any impossible values.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical tests are named, exact p-values and CIs are reported, effect sizes with CIs are provided, software is identified, and data presentation is appropriate for a clinical trial. Mathematical plausibility was checked and no inconsistencies were found.

Evidence

direct quote[Table 2 and Figure 2]

“Treatment difference −534.11 (−668.20 to −400.02), P < 0.0001”

direct quote[Methods, Statistical methods]

“Analyses were carried out using SAS Enterprise Guide v.8, unless stated otherwise.”

PASSReviewer 2· 85% conf

Statistical methods are adequately described and reported, with named tests, effect sizes with CIs, and software identified; exact p-values are generally provided.

Evidence

direct quote[Methods, 'Statistical methods']

“The primary outcome was analyzed using an analysis of covariance with treatment as fixed effect, and baseline BMI stratum and baseline energy intake as covariates.”

direct quote[Results, 'Primary outcome']

“treatment difference −534.1 kcal (95% confidence interval (CI) −668.2 to −400.0, P < 0.0001)”

direct quote[Table 2]

“Versus placebo – – −534.11 (−668.20 to −400.02), P < 0.0001”

WARNReviewer 3· 85% conf

Statistical tests are named, exact p-values and CIs are reported extensively, software is identified, and data presentation is adequate (least squares means with SE/CIs, per-group n). However, assumptions for the primary ANCOVA (normality, homogeneity of variance) are not explicitly verified, and there is no pre-specified multiplicity adjustment for secondary outcomes, though this is discussed as a limitation.

Evidence

direct quote[Results, Primary outcome; Table 2]

“The prespecified primary analysis using an analysis of covariance found a statistically significantly greater mean change from baseline to week 3 in energy intake … treatment difference −534.1 kcal (95% confidence interval (CI) −668.2 to −400.0, P < 0.0001)”

absence[Methods, Statistical methods; Results]

No formal verification of ANCOVA assumptions (normality, homogeneity) is reported.

direct quote[Methods, Statistical methods]

“Analyses were carried out using SAS Enterprise Guide v.8, unless stated otherwise.”

Data availability statement is reported and adequate: it states that individual participant data can be accessed through Vivli after a proposal and data-sharing agreement, with a link to instructions. Source data for figures are provided as supplementary files. No code deposition is needed as standard software was used. All applicable sub-criteria are satisfied.

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

A data availability statement is provided that describes a concrete managed-access platform (Vivli) with conditions. Repository deposit and accession numbers are not applicable for patient-level data. No custom code was created, so code sharing is not applicable.

Evidence

direct quote[Data availability]

“For details on submitting a request, see the instructions provided at www.vivli.org.”

PASSReviewer 2· 90% conf

A detailed data availability statement is provided with a concrete access mechanism via Vivli, meeting adequacy for patient-level data.

Evidence

direct quote[Data availability section]

“Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, except for 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.”

WARNReviewer 3· 80% conf

A data availability statement is present and describes a concrete managed-access route via Vivli with conditions and timeframe, meeting the adequate standard. However, no code is shared, and source data for figures are provided as supplementary files.

Evidence

direct quote[Data availability section]

“Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, except for pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data have been 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.”

absence[Data availability section; entire paper]

No code sharing statement or repository URL is provided.

Methods are comprehensive with references to supplementary material. Trial registration number (NCT04311411) is provided. A Nature Portfolio reporting summary is included. All pre-specified outcomes are reported, including null findings for some fMRI contrasts. Limitations are explicitly discussed (e.g., open-label comparator, sex imbalance, multiplicity). Conclusions are appropriately cautious. Funding and competing interests are fully disclosed.

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 manuscript is well-structured: methods are detailed, trial is registered, a reporting summary is provided, all outcomes (including negative) are reported, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Abstract and Methods]

“ClinicalTrials.gov registration: NCT04311411 https://clinicaltrials.gov/ct2/show/NCT04311411”

direct quote[Discussion]

“First, the absence of a blinded comparison to a long-acting GLP-1 RA. ... Second, a lack of sex parity in the study... Third, this study was principally designed to detect treatment effect of the primary outcome. Since type 1 error rate adjustments were not made for multiple comparisons...”

direct quote[Acknowledgements and Competing interests]

“This study was funded by Eli Lilly and Company. ... S.S., H.N., A.K., S.U., L.B., E.P., A.H., M.M., D.O.S., Z.M. and T.C. are employees and shareholders of Eli Lilly and Company.”

PASSReviewer 2· 95% conf

The manuscript is transparent and complete: methods are detailed, trial is registered, a reporting checklist is used, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Abstract and Methods]

“ClinicalTrials.gov registration: NCT04311411”

direct quote[Discussion, paragraph 10]

“There were several study limitations. First, the absence of a blinded comparison to a long-acting GLP-1 RA. Second, a lack of sex parity... Third, this study was principally designed to detect treatment effect of the primary outcome. Since type 1 error rate adjustments were not made for multiple comparisons...”

direct quote[Acknowledgements and Competing interests]

“This study was funded by Eli Lilly and Company. ... Competing interests ... [detailed]”

PASSReviewer 3· 90% conf

The manuscript is comprehensively reported: methods are detailed for replication, trial registration is provided (NCT04311411), a reporting guideline is referenced (Nature Portfolio reporting summary), all outcomes (including null) are reported, limitations are thoroughly discussed, conclusions are proportional to the evidence, and funding/COI statements are complete.

Evidence

direct quote[Abstract; Methods, Study design]

“This study is registered with ClinicalTrials.gov, NCT04311411”

direct quote[Discussion, paragraph 10]

“There were several study limitations. First, the absence of a blinded comparison to a long-acting GLP-1 RA. … Second, a lack of sex parity in the study … Third, this study was principally designed to detect treatment effect of the primary outcome. Since type 1 error rate adjustments were not made for multiple comparisons …”

direct quote[Acknowledgements; Competing interests]

“This study was funded by Eli Lilly and Company. … Competing interests: The institution of C.K.M. is supported by NORC Center Grant P30 DK072476 … S.S., H.N., A.K., S.U., L.B., E.P., A.H., M.M., D.O.S., Z.M. and T.C. are employees and shareholders of Eli Lilly and Company.”

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

Checked 57 references: 2 verified — 55 unresolved.

Reproducibility

3 data/code links checked; 3 live.

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

Adcurare Rigor Action ItemsFinal pass before journal submission

The published paper is methodologically sound but has several reporting gaps that an informed reader should weigh: the open-label comparator, missing assumption verification, two inconsistent p-values, and no code sharing. These issues do not invalidate the primary findings but warrant a correction or independent re-analysis for the inconsistent p-values.

1.
HIGHstatistics
In the Results section, correct the two inconsistent p-values: for adverse events (tirzepatide vs placebo) the reported p=1e-10 should be p=0.00096; for discontinuation due to AE the reported p=0.1 should be p=0.67.
The statistics verification component found these p-values to be inconsistent with recomputed values, which could indicate a reporting error.
2.
HIGHreporting
In the Methods (Statistical methods), add a statement verifying that the assumptions of ANCOVA (normality of residuals, homogeneity of variance) were checked, or note that robust standard errors were used.
Standard reporting expectations for ANCOVA require assumption verification; its absence is a common reviewer objection.
3.
HIGHdata code
Add a code sharing statement to the Data availability section, and deposit the SAS analysis scripts (e.g., for the primary ANCOVA and MMRM) in a public repository (e.g., GitHub, Zenodo) with a persistent DOI.
Reproducibility requires access to the analysis code; the current paper provides no code sharing statement.
4.
HIGHreporting
In the Methods (Procedures), explicitly state the manufacturer/source for tirzepatide, liraglutide, and placebo (e.g., 'Eli Lilly and Company, Indianapolis, IN, USA').
The source of investigational products is essential for reproducibility; currently it is only implied by the funding disclosure.
5.
HIGHreporting
In the Methods (Randomization and masking), describe the method used to generate the randomization table (e.g., computer-generated random number sequence) and who generated the allocation sequence.
A vague description of the randomization method reduces transparency and confidence in the allocation concealment.
6.
HIGHreporting
In the Methods (Statistical methods), pre-specify the approach for handling outliers (e.g., exclusion based on predefined SD thresholds or sensitivity analyses).
The absence of a pre-specified outlier handling plan weakens the analytic rigor.
7.
MEDIUMreporting
In Table 2, clarify whether the reported percentage change (e.g., −72.4% for tirzepatide at week 6) is the median percent change from baseline or the LS mean percent change, and place it in a separate column.
The copyedit report flagged this as confusing; the percentage appears inconsistent with the absolute change if interpreted as an LS mean.
8.
MEDIUMreporting
In the Results (Primary outcome), specify the figure references: 'Fig. 2b and Extended Data Fig. 1' instead of the ambiguous 'Fig. and Extended Data Fig.'.
The copyedit report noted that the figure references are ambiguous without specific labels.
9.
MEDIUMreporting
In the Abstract, consider specifying the direction of impact for tirzepatide on food intake (e.g., 'by reducing appetite and food cravings').
The copyedit report suggested this minor clarity improvement.
10.
MEDIUMreporting
In the Abstract footnote for VAS, rephrase 'A higher overall appetite score indicated lower appetite' to 'A higher overall appetite score indicates less appetite' for clarity.
The copyedit report noted this is a clarity improvement.
11.
MEDIUMreporting
In the Author contributions, change 'approved of this paper to be submitted for publication' to 'approved this paper for submission'.
The copyedit report flagged this as a minor grammar issue.
12.
LOWreporting
For p-values reported as '<0.0001', consider providing the exact value to four decimal places in supplementary tables to enable precise assessment of significance.
Exact p-values are preferred for transparency, though '<0.0001' is acceptable for very small values.
13.
LOWreporting
In the limitations section, explicitly recommend that future studies with balanced sex representation investigate sex-specific effects, given the sex imbalance across treatment groups.
The sex imbalance is already acknowledged; a specific recommendation would strengthen the discussion.

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Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial

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DOI

10.1038/s41591-025-03774-9

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