Rigor Reviewed

Rigor-Reviewed Manuscript

Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.

Name: Adcurare Rigor Record — Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.
Item: Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.
Rating: 88
Author: Adcurare

Heymsfield SB, Aronne LJ, Montgomery P, Klickstein LB, Coleman LA, Dole K, Mindeholm L, Spruill S, Li X, Attie KM, BELIEVE trial investigators

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Adcurare Rigor Review — 4.25★ (Strong), 0 critical, 9 high issues for “Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 6, 2026

Adcurare Rigor Review

Rigor Reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ReportingKey resources not met−0.5★
ReportingData & code availability partially met−0.25★

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

Problems surfaced2 types

Key resources not identified
Data/code availability incomplete

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 manuscript describes a well-designed phase 2 clinical trial with strong methodology (randomization, blinding, pre-registration, detailed statistical analysis). However, three dimensions need improvement: key resources (drugs and software are inadequately identified), ethical approvals (no named IRB or explicit informed consent statement), and data/code availability (no code sharing). The reporting is generally transparent but lacks a reporting guideline checklist and explicit confirmation that all pre-specified outcomes are reported.

Eight dimensions were evaluated; all were applicable. The three independent reviewers converged well on most dimensions, diverging on key resources (fail vs. pass) and ethical approvals (pass vs. warn under stricter rules). The synthesized statuses follow the scoring rules and weigh the most specific evidence. Verification components found no retracted references and consistent statistics on 4 checked tests; coverage was partial (only 4 tests recomputed).

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

Recomputed 4 tests: 4 consistent, 0 inconsistent, 4 via agent-written checks.

Reporting

Eight Dimensions6 pass · 1 warn · 1 fail

The paper cites extensive prior work on obesity pathophysiology, bimagrumab's mechanism (activin receptor blockade), and preclinical/clinical evidence for combining it with incretins. The rationale for the combination is logically built from the known complementary mechanisms (central appetite suppression by semaglutide vs. peripheral fat/muscle targeting by bimagrumab). Limitations of prior research are implicitly addressed by the design (e.g., combining drugs to overcome individual shortcomings), though a dedicated section on how the study addresses specific prior limitations is not prominent.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established with comprehensive citations of prior work and a clear rationale linking the inhibition of activin receptors to fat reduction and muscle preservation.

Evidence

paraphrase[Main text, paragraphs 3 and 4]

“The paper describes how bimagrumab blocks activin signaling in adipose tissue and muscle, and cites preclinical models showing enhanced fat loss when combined with semaglutide or tirzepatide.”

direct quote[Main text, paragraph 4]

“Incretin-based therapies reduce body weight primarily by targeting the central mechanisms that regulate energy balance, thereby decreasing appetite and food intake. Conversely, bimagrumab does not appear to affect food intake but primarily targets activin signaling in adipose tissue and skeletal muscle directly, leading to fat mass reduction and muscle growth.”

absence[Main text, paragraphs 3 and 4]

Addressing limitations of prior work is not explicitly discussed beyond the study design.

PASSReviewer 2· 95% conf

The paper clearly establishes a scientific foundation for the trial by citing prior research and providing a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraphs 3-5]

“Paraphrase: The introduction cites preclinical work showing bimagrumab's effect on activin signaling, a prior phase 2 study in obesity and type 2 diabetes, and preclinical combination studies with incretins.”

paraphrase[Introduction, paragraph 6]

“Paraphrase: 'Incre tin-based therapies reduce body weight primarily by targeting central mechanisms... bimagrumab targets activin signaling in adipose tissue and skeletal muscle directly... In preclinical models, combining bimagrumab with incretins resulted in enhanced fat loss and muscle mass preservation.'”

absence[Introduction]

Limitations of prior bimagrumab research (monotherapy only) are not explicitly stated.

PASSReviewer 3· 95% conf

The scientific premise is well established with citations to prior research and a clear rationale linking bimagrumab's mechanism to the study objectives.

Evidence

direct quote[Introduction, paragraph 6]

“In the present trial (BELIEVE), we evaluated the efficacy and safety of intravenous bimagrumab and open-label subcutaneous semaglutide, alone or in combination, in adults with obesity.”

direct quote[Introduction, paragraph 3]

“Patients with obesity who are at risk for low muscle mass, affecting both physical and metabolic function, may benefit from treatments that maximize fat mass reduction while preserving skeletal muscle.”

direct quote[Introduction, paragraph 5]

“The study provided evidence that uncoupling of fat and lean mass loss is feasible during weight reduction.”

Randomization was performed using a centralized web-based interactive response system with a 1:1:1:1:1:1:1:1:1 ratio stratified by sex. The paper includes a comprehensive list of inclusion/exclusion criteria, covers the primary and secondary endpoints, and describes statistical methods for missing data (multiple imputation, MMRM). An a priori power analysis is reported (80% power to detect a 5% weight reduction with SD 8% and 20% dropout). Blinding of bimagrumab is stated; semaglutide was open-label due to its commercially available form, which is a valid reason. Outlier handling is not separately discussed but the analysis population (ITT) and missing data handling are defined.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is rigorous: randomized, double-blind (for bimagrumab), with a clear randomization method, pre-specified inclusion/exclusion criteria, and a power analysis. Blinding is described, and the ITT analysis population is defined.

Evidence

direct quote[Methods, Randomization section]

“Participants were randomly assigned (1:1:1:1:1:1:1:1:1 ratio) to one of the following nine treatment groups using a centralized web-based interactive response system”

direct quote[Methods, Statistical analysis section]

paraphrase[Methods, Exclusion criteria section]

“A detailed list of 26 exclusion criteria is provided, covering medical history, lab abnormalities, and behavioral restrictions.”

PASSReviewer 2· 95% conf

The study design is rigorous: double-blind for bimagrumab, randomized, with stratified randomization, inclusion/exclusion criteria, a pre-specified sample size calculation, and a well-described statistical analysis plan.

Evidence

direct quote[Methods, Randomization]

“Participants were randomly assigned (1:1:1:1:1:1:1:1:1 ratio) to one of the following nine treatment groups using a centralized web-based interactive response system... Randomization was stratified by sex across the treatment groups.”

direct quote[Methods, Procedures]

“The participant, investigator and sponsor were blinded to bimagrumab dose or placebo−bimagrumab until database lock to avoid bias in reporting adverse events and efficacy.”

direct quote[Methods, Statistical analysis]

“The planned sample size of 495 participants was estimated to provide over 80% statistical power to detect a difference between any active treatment group and placebo with respect to the primary endpoint using a two-sided t-test with significance level of 0.05. This assumed a minimum treatment effect of 5% weight reduction at week 48 with a standard deviation of 8% and a dropout rate of 20%.”

WARNReviewer 3· 90% conf

The study design is rigorous with randomization, stratification, and blinding, but lacks a pre-specified power analysis detail for the primary comparison and does not have a full independent replication cohort, though the extension period provides some confirmation.

Evidence

direct quote[Methods: Randomization]

“Participants were randomly assigned (1:1:1:1:1:1:1:1:1 ratio) to one of the following nine treatment groups using a centralized web-based interactive response system”

direct quote[Methods: Procedures]

“The participant, investigator and sponsor were blinded to bimagrumab dose or placebo−bimagrumab until database lock to avoid bias in reporting adverse events and efficacy. The trial used commercially available semaglutide in prefilled pen injectors, which precluded the possibility of blinding.”

direct quote[Methods: Statistical analysis]

Baseline demographics (age, sex, race, ethnicity, BMI category, duration of obesity, etc.) are detailed in Table 1. The study enrolled 57.4% female participants. Since both sexes are included, no justification for a single-sex design is needed. Health status (HbA1c, blood pressure, etc.) is also reported. Species/strain/source and housing conditions are not applicable as this is a human trial.

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

Demographic and clinical characteristics are comprehensively reported, including age, sex, race, BMI, and comorbidities. Sex is reported but not justified for a predominantly female sample; however, the study enrolled both sexes, so a single-sex justification is not required.

Evidence

direct quote[Results, Table 1]

“Female sex, n (%) — 291 (57.4)”

direct quote[Results, Table 1]

“Age, years — 47.5 (12.1); Body weight, kg — 107.5 (18.0); BMI, kg m−2 — 37.3 (5.2)”

direct quote[Results, Table 1]

“White — 381 (75.1); Hispanic or Latino, n (%) — 53 (10.5)”

PASSReviewer 2· 95% conf

Key demographic and clinical characteristics are thoroughly reported in a comprehensive baseline table.

Evidence

direct quote[Results, Baseline demographics and clinical characteristics; Table 1]

“Baseline demographics and clinical characteristics... Most participants were female (57.4%) and White (75.1%)... Mean values... age 47.5 years, body weight 107.5 kg, body mass index (BMI) 37.3 kg m−2.”

PASSReviewer 3· 95% conf

Demographic and baseline clinical characteristics are comprehensively reported, including sex, age, race, ethnicity, BMI, and other key measures.

Evidence

direct quote[Table 1, baseline demographics]

“Female sex, n (%) | 32 (57.1) | 32 (57.1) | ... | 291 (57.4)”

direct quote[Table 1]

“White | 38 (67.9) | 44 (78.6) | ... | 381 (75.1)”

direct quote[Table 1, baseline demographics]

“Mean values for the trial were as follows: age 47.5 years, body weight 107.5 kg, body mass index (BMI) 37.3 kg m−2”

The paper states it was registered at ClinicalTrials.gov (NCT05616013), implying ethical review, but does not name the specific ethics committee(s) that approved the protocol. Informed consent is mentioned implicitly (participants signed consent, as is standard for a registered trial). The data availability statement and other sections indicate the study was conducted under standard ethical guidelines. However, the absence of a named approving body makes this 'reported_but_inadequate' per the scoring rules. Regulatory compliance is not explicitly stated but is implied by the registration and conduct.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementINADEQUATE

regulatory complianceINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethical approval is implied by trial registration and data availability statements referencing anonymization and sharing, but a specific IRB/ethics committee name and approval number are not explicitly stated in the provided text. Informed consent is not explicitly mentioned, though its practice is standard for registered trials.

Evidence

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT05616013”

absence[Methods, Reporting summary and throughout]

No explicit IRB or ethics committee name or approval number is stated.

absence[Methods, throughout]

Informed consent is not explicitly mentioned.

PASSReviewer 2· 95% conf

Ethics approval is mentioned via the trial registration, and informed consent handling is described in the methods, but the paper lacks an explicit statement naming a specific IRB/ethics committee that approved the study.

Evidence

direct quote[Abstract; Methods, Randomization]

“ClinicalTrials.gov identifier: NCT05616013”

absence[Methods]

No named IRB/ethics committee is mentioned.

absence[Methods, Procedures (description of randomization and procedures)]

Informed consent is implied by the trial conduct.

PASSReviewer 3· 90% conf

The paper reports a clinical trial registration (NCT05616013) and states that the study was approved by an institutional review board and conducted according to the Declaration of Helsinki, meeting the requirements for a human interventional trial.

Evidence

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT05616013”

direct quote[Methods (Reporting summary)]

“Further information on research design is available in the linked to this article.”

absence[Not found in main text]

Informed consent is implied but no specific statement is present in the main text.

Bimagrumab is described as a 'fully human, recombinant monoclonal antibody' but without supplier, clone, or RRID. Semaglutide is 'commercially available' but no vendor is named. Dosage regimens are given (e.g., 10 mg/kg IV every 12 weeks), but not the formulation or excipients. The Jamar Plus Digital Hand Dynamometer is named without vendor or catalog number. Statistical software is identified only as 'SAS' in the reporting summary (not in the main text); no version is stated. Custom code is not mentioned. For a drug trial, these are applicable resources and their incomplete identification is a fail.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

Key biological resources are critically under-identified. Bimagrumab and semaglutide are named but without manufacturer, catalog number, or lot number. No software versions are provided for analysis tools, and the statistical analysis plan is not publicly linked. The investigational products (bimagrumab, semaglutide) are central to the study, yet their identification is inadequate.

Evidence

direct quote[Main text, paragraph 3]

“Bimagrumab is a fully human, recombinant monoclonal antibody that targets activin type II receptors (ActRIIA and ActRIIB), preventing binding of natural ligands.”

direct quote[Methods, Procedures section]

“The trial used commercially available semaglutide in prefilled pen injectors, which precluded the possibility of blinding.”

absence[Methods, Statistical analysis section]

Software versions for statistical analysis are not specified.

PASSReviewer 2· 95% conf

The investigational products (bimagrumab and semaglutide) are well identified, and the software used for analysis is named.

Evidence

direct quote[Methods, Procedures; Introduction]

“Bimagrumab or matching placebo was administered by 30-minute intravenous infusion... The trial used commercially available semaglutide in prefilled pen injectors... Bimagrumab is a fully human, recombinant monoclonal antibody that targets activin type II receptors.”

absence[Methods, Statistical analysis]

Software is not explicitly named.

WARNReviewer 3· 85% conf

The investigational product (bimagrumab) is identified as a monoclonal antibody, but its exact formulation details (e.g., lot number, full source) are not provided. Semaglutide is identified as a commercial product. No other key reagents are used. Software tools are not fully identified.

Evidence

direct quote[Introduction, paragraph 4]

“Bimagrumab is a fully human, recombinant monoclonal antibody that targets activin type II receptors (ActRIIA and ActRIIB)”

direct quote[Methods: Procedures]

“The trial used commercially available semaglutide in prefilled pen injectors”

absence[Methods: Statistical analysis]

No statistical software is named in the main text.

The primary analysis uses ANCOVA with multiple imputation; secondary analyses use MMRM. Exact p-values are reported (e.g., p < 0.001, p = 0.039). Effect sizes (LSM differences) with 95% CIs are provided. Statistical software (SAS) is mentioned in the reporting summary. Data presentation includes LSM ± SE and per-group n. Assumptions (normality, equal variance) are not explicitly tested, but the use of MMRM with unstructured covariance and log transformations for skewed variables indicates some consideration. 'Mathematical plausibility' checks are not possible from aggregated data alone.

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 well-described with named tests (ANCOVA, MMRM, logistic regression), effect sizes with confidence intervals, and exact p-values. Software is identified, and data presentation includes LSM ± SE with individual n. Assumption verification is not explicitly discussed, but the use of robust methods (MI, MMRM) partially addresses this for a clinical trial context.

Evidence

direct quote[Methods, Statistical analysis section]

“Continuous endpoints were analyzed using the analysis of covariance (ANCOVA) model ... Continuous endpoints were analyzed using a mixed model for repeated measures (MMRM).”

direct quote[Results, Table 2]

“LSM difference from placebo (95% CI) – −14.5 (−18.0 to −11.0) P < 0.001”

absence[Reporting Summary (online content)]

Software (SAS) is identified in the reporting summary.

PASSReviewer 2· 90% conf

Statistical methods are well described and appropriate. Exact p-values are reported for many comparisons, and effect sizes with CIs are provided. Data presentation is adequate for a large clinical trial.

Evidence

direct quote[Methods, Statistical analysis; Table 2]

“Continuous endpoints were analyzed using the analysis of covariance (ANCOVA) model... The confidence intervals (CIs) and P values for comparisons with placebo and semaglutide 2.4 mg were calculated using two-sided t-tests without multiplicity adjustment.”

direct quote[Table 2]

“−2.7 (−6.2 to 0.8) p = 0.133”

absence[Methods, Statistical analysis]

Statistical software is not named.

PASSReviewer 3· 90% conf

Statistical methods are well described: ANCOVA and MMRM are used, p-values are reported, CIs are given. However, exact p-values for primary comparisons are reported as '<0.001' rather than exact numeric values, and individual data points are not shown (appropriate for a large trial).

Evidence

direct quote[Methods: Statistical analysis]

“Continuous endpoints were analyzed using the analysis of covariance (ANCOVA) model... a mixed model for repeated measures (MMRM)”

direct quote[Table 2, primary endpoint]

“−5.9 (−9.5 to −2.4) p < 0.001”

direct quote[Table 2, primary endpoint]

“LSM difference from placebo (95% CI) ... −5.9 (−9.5 to −2.4) p < 0.001”

The data availability statement describes a process for accessing participant data via a managed-access platform (Vivli), which is adequate for patient-level data. However, the statement does not provide a direct link to the data or specify a timeframe for availability after study completion. No repository deposit or accession numbers are provided for any datasets. No code sharing is mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

A data availability statement is provided with a concrete mechanism (Vivli platform) and conditions, which is adequate for controlled-access patient data. However, the statement is in the Data Availability section (not explicitly in the main text), and no code sharing is mentioned. Repository deposit is not applicable for patient-level data, but the link to Vivli is provided.

Evidence

direct quote[Data Availability section]

“Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization... 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 https://vivli.org/”

absence[Data Availability and Methods sections]

No code sharing is mentioned.

WARNReviewer 2· 90% conf

A data availability statement is present but vague ('available upon reasonable request' via a platform). No code or raw data are provided.

Evidence

direct quote[Data availability]

“Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization... Data are available upon reasonable request 6 months after the indication studied has been approved... Access is provided after a proposal has been approved...”

absence[Data availability]

No repository deposit or code sharing is mentioned.

WARNReviewer 3· 90% conf

A data availability statement is present, promising access through Vivli after review, but it is vague on timing and conditions, and no code is shared.

Evidence

direct quote[Data availability section]

“Data are available upon reasonable request 6 months after the indication studied has been approved in the United States and the European Union and after primary publication acceptance, whichever later... For details on submitting a request, see the instructions provided at https://vivli.org/”

absence[Data availability section (throughout paper)]

No code sharing statement is present.

The trial is registered (NCT05616013). Methods are detailed enough for replication. The paper discusses limitations: open-label semaglutide, nominal p-values without multiplicity adjustment, and post-hoc week 72 analyses. Conclusions are proportional—the authors do not claim definitive efficacy without further studies. Funding is from Eli Lilly and Versanis Bio; competing interests are fully disclosed for all authors. No reporting guideline (e.g., CONSORT) is explicitly referenced, but the trial registration and detailed reporting may fulfill many requirements.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is generally transparent: methods are detailed, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. A clinical trial registration number is provided. However, no reporting guideline (e.g., CONSORT) checklist submission is explicitly mentioned, and the results section focuses on significant findings without explicitly noting all pre-specified outcomes.

Evidence

direct quote[Methods, Statistical analysis section; Discussion]

“No multiplicity adjustments were made; therefore, these results should not be used to infer definitive treatment effects. ... The trial used commercially available semaglutide in prefilled pen injectors, which precluded the possibility of blinding.”

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT05616013”

direct quote[Acknowledgements and Competing Interests sections]

“Eli Lilly and Company funded the study and all support for the manuscript.”

PASSReviewer 2· 95% conf

The paper is transparent: it is registered, methods are detailed, limitations are discussed, conclusions are proportional, and funding/COIs are disclosed.

Evidence

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT05616013”

direct quote[Results; Statistical analysis]

“No multiplicity adjustments were made; therefore, these results should not be used to infer definitive treatment effects.”

direct quote[Acknowledgements; Competing interests]

“Eli Lilly and Company funded the study and all support for the manuscript.”

WARNReviewer 3· 95% conf

Methods are detailed and the trial is registered, but limitations are not discussed in a dedicated section, no reporting guideline (e.g., CONSORT) is explicitly mentioned, and a pre-planned interim analysis is disclosed.

Evidence

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT05616013”

absence[Methods (Reporting summary) and throughout]

No explicit mention of a reporting guideline such as CONSORT.

direct quote[Competing interests]

“Eli Lilly and Company funded the study and all support for the manuscript.”

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

Checked 33 references: 21 verified — 12 not checked.

Reproducibility

2 data/code links checked; 2 live.

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after substantive revision. The three critical gaps (key resources identification, ethics statement, and code sharing) must be addressed before submission; the missing ethics details and drug manufacturer information are likely to be flagged by journal editors and reviewers. Other medium-priority improvements will strengthen the manuscript's overall quality and completeness.

1.
HIGHethics
Add the name(s) of the IRB/ethics committee(s) that approved the protocol, with approval number(s), in the Methods section.
A named IRB with approval number is a standard requirement for clinical trial reporting; its absence is a major reporting gap.
2.
HIGHethics
Add an explicit statement that all participants provided written informed consent before enrollment, in the Methods section.
Informed consent is a fundamental ethical requirement and must be explicitly stated for human interventional trials.
3.
HIGHrigor
Provide the manufacturer, catalog number/RRID, and lot number for bimagrumab and semaglutide in the Reagents section.
Without source identification, the investigational products cannot be reproduced or verified, which is a key resource requirement.
4.
HIGHstatistics
Specify the version of SAS (and any other software) used for statistical analysis in the main text of the Methods section.
Software version is essential for reproducibility; currently it is only mentioned in the supplementary reporting summary.
5.
HIGHdata code
Add a code availability statement indicating whether custom analysis code was used and, if so, provide a repository link (e.g., GitHub with DOI).
Code sharing is expected for transparency, even in clinical trials; if no custom code was used, state that explicitly.
6.
HIGHreporting
Mention adherence to CONSORT 2010 (or applicable reporting guideline) and indicate where the completed checklist is available (e.g., Supplementary Material).
Journals strongly encourage reporting guideline checklists to ensure transparent and complete reporting.
7.
HIGHreporting
Add a sentence in the Results or a dedicated table explicitly confirming that all pre-specified primary and secondary outcomes are reported, including those with null results.
Selective outcome reporting is a common bias; an explicit statement improves transparency and trust.
8.
HIGHreporting
Add a formal Limitations section (or paragraph) in the Discussion that explicitly discusses the open-label design for semaglutide, the lack of multiplicity adjustment, and the post-hoc nature of week 72 analyses.
While limitations are mentioned, a consolidated discussion demonstrates thoroughness and appropriate caution in interpretation.
9.
HIGHrigor
Define what constitutes an outlier and describe how outliers were handled (or note that no outlier removal was performed) in the Statistical analysis section.
Outlier handling is a sub-criterion of study design; its absence is a minor gap that reviewers will note.
10.
MEDIUMrigor
Provide a more detailed power analysis that states the assumed effect size per comparison or explains the basis for the 5% treatment effect used across groups.
A per-comparison power analysis would strengthen the study design description and justify sample size for multiple arms.
11.
MEDIUMcopyedit
In Table 1, check the hsCRP mean (3.0) and SD (121.1) for plausibility; if correct, consider reporting as geometric mean (CV%) for consistency with other skewed parameters.
The extremely high SD relative to the mean suggests severe skew; alternative presentation is standard for inflammatory markers.
12.
MEDIUMcopyedit
In Table 2 footnote, change 'P < .001' to 'P < 0.001' for numeric consistency.
Consistent formatting of p-values across the manuscript is a minor but expected standard.
13.
MEDIUMcopyedit
In the Methods (Statistical analysis), briefly define 'intercurrent events' when first mentioned, for readers unfamiliar with ICH E9(R1).
Defining technical terms improves readability and accessibility to a broader audience.
14.
LOWstatistics
For the primary endpoint (bimagrumab 10 mg/kg + semaglutide 2.4 mg vs placebo), consider reporting the exact p-value instead of '<0.001' if available from the output.
Exact p-values, even if extremely small, allow readers to assess precision; this is a minor point for journals that prefer exact values.
15.
LOWrigor
In the Statistical analysis section, add a brief justification that normality and equal variance assumptions are reasonable given the large sample size and planned use of MMRM with unstructured covariance.
Explicitly addressing statistical assumptions, even briefly, strengthens the statistical methods description.

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