Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.
Pratley RE, Denham DS, Trivedi R, Watkins E, Connery L, Barnes J, Yu D, Hong J, Simard C, Umans K, Liu L, Tirucherai GS, Marantz JL
- DOI
- 10.1038/s41591-026-04440-4
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-21
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/a9a432b0-63cc-4562-a391-aa62533ff844 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×4−2★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingData & code availability partially met−0.25★
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary endpoint is change in lean body mass measured by DEXA, which is a surrogate for clinical outcomes such as physical function or health. Although the paper shows target engagement via increased latent myostatin levels, it does not cite validated evidence linking lean mass preservation to improved clinical outcomes in this context.
“Apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo.”
- 02Treatment effect not shown to be clinically meaningful
The primary effect is a 1.9 kg difference in lean mass loss, which is a small fraction of total lean mass (baseline ~48-50 kg) and is not anchored to a minimal clinically important difference or functional benefit. The paper does not provide evidence that this magnitude of lean mass preservation translates to meaningful clinical outcomes.
“Apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo.”
- 03Other integrity concern
Trial NCT06445075 was first submitted to ClinicalTrials.gov on 2024-05-22, after the registered study start date of 2024-05-21. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT06445075
reviewer’s wording
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.
This is a well-conducted and well-reported phase 2 randomized controlled trial with a clear scientific premise, rigorous design, and transparent reporting. The main weaknesses are a vague data availability statement and minor reporting gaps (outlier handling, model assumptions, explicit reporting guideline).
Both reviewers classified the study as interventional and agreed on all dimension statuses; no divergence required reconciliation. The statistics verification recomputed only 2 tests (those with test statistics/df or effect+CI); the rest of the statistical results are unverified. The citation check found no retracted or unresolved references. The preregistration check confirmed registration on ClinicalTrials.gov, but the integrity check noted the registration was submitted after the study start date (retrospective registration).
Numerical inconsistencies
1 finding · worst lowValues 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.
- Internal contradictions in the reported numbersAssessed
Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.
- CONSISTENTreported p = .001 · recomputed p = <.001Reviewers 1, 2Primary endpoint p-value from difference and 80% CI
“At week 24, apitegromab treatment significantly reduced lean mass loss, preserving 1.9 kg (1.2−2.7, least square means (80% confidence interval (CI))) of lean mass compared to placebo (nominal, P = 0.0014).”
Taken as given: The 1.9 is the difference in least square means.; The 1.2 and 2.7 are the lower and upper bounds of the 80% CI.; The CI is two-sided at 80%.; The p-value is two-sided from a t-test.Method: Recomputed two-sided p-value from the difference and 80% CI using the t-distribution approximation.How we recomputed it: pCI(1.9, 1.2, 2.7, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Percentage of total loss due to lean mass loss p-value
“Percentage of total loss due to lean mass loss (%) (80% CI) | 14.6 (10.5, 18.7) | 30.2 (26.4, 33.9) | −15.6 (−19.8, −11.4) | <0.0001”
Taken as given: The -15.6 is the difference in least square means.; The -19.8 and -11.4 are the lower and upper bounds of the 80% CI.; The CI is two-sided at 80%.; The p-value is two-sided from a t-test.Method: Recomputed two-sided p-value from the difference and 80% CI using the t-distribution approximation.How we recomputed it: pCI(-15.6, -19.8, -11.4, 0)
- lowinternal contradictionThe abstract reports P = 0.001 for the primary endpoint, while the results section and Table 2 report P = 0.0014. This is a minor inconsistency in rounding.
Abstract: 'P = 0.001'; Results: 'P = 0.0014'
Abstractreviewer’s wording
Overstated conclusions
2 findings · worst highConclusions 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
8 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewer 1Apitegromab preserved lean mass compared with placebo during tirzepatide-induced weight loss.The primary endpoint result (1.9 kg difference, P=0.0014) directly supports this claim.Evidence: Primary endpoint: change in lean mass at week 24, difference 1.9 kg (80% CI 1.2-2.7), P=0.0014.
At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001)
Abstractreviewer’s wording - supportedReviewers 1, 2Apitegromab was well tolerated with similar safety profile to placebo.AE and SAE rates were similar between groups, supporting tolerability.Evidence: AE incidence 76% vs 71%, SAE 2% vs 2%, no drug-related SAEs.
“Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively.”
ResultsFind in source - supportedReviewer 1Apitegromab achieved target engagement as shown by increased latent myostatin.Pharmacodynamic data show increased latent myostatin levels, supporting target engagement.Evidence: Latent myostatin increased and plateaued by week 16.
In these participants, concentrations of latent myostatin, a pharmacodynamic marker, increased substantially after the first dose, achieved a plateau at approximately week 16 and remained consistently elevated throughout the treatment period, demonstrating successful target engagement.
Resultsreviewer’s wording - supportedReviewer 1The study provides proof of concept for selective myostatin inhibition in preserving lean mass.The primary endpoint and supportive analyses support proof of concept, though the study is phase 2 and not definitive.Evidence: Primary endpoint met, with consistent post hoc analyses.
“Results from EMBRAZE demonstrate clinical proof of concept for a highly selective antimyostatin antibody to preserve lean mass with tirzepatide therapy.”
DiscussionFind in source - supportedReviewer 2Apitegromab preserved lean mass during tirzepatide-induced weight loss.The primary endpoint showed a statistically significant difference in lean mass change favoring apitegromab, with a reported p-value of 0.0014.Evidence: Primary endpoint: change in lean mass at week 24, difference 1.9 kg (80% CI 1.2-2.7), P=0.0014.
“apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo ( P = 0.001)”
AbstractFind in source - supportedReviewer 2Apitegromab achieved target engagement as shown by increased latent myostatin levels.Latent myostatin levels increased and plateaued, indicating target engagement.Evidence: Extended Data Fig. 1 shows increased latent myostatin over time.
“concentrations of latent myostatin, a pharmacodynamic marker, increased substantially after the first dose, achieved a plateau at approximately week 16”
ResultsFind in source - supportedReviewer 2The effect of apitegromab on lean mass preservation is durable at week 32.The difference remained significant at week 32, though the effect size was smaller.Evidence: Week 32 difference 0.9 kg (80% CI 0.3-1.5), P=0.0480.
“At this timepoint, the difference in lean mass between apitegromab and placebo remained significant (least square mean (80% CI), 0.9 (0.3−1.5); nominal, P = 0.0480; Fig. )”
ResultsFind in source - supportedReviewer 2Apitegromab is the first study to demonstrate efficacy of apitegromab in adults over 21 years of age.The paper states this is the first study in this population, and the results support efficacy.Evidence: The study enrolled adults aged 18-65 and showed significant lean mass preservation.
“To our knowledge, EMBRAZE marks the first study with participants over 21 years of age to demonstrate the efficacy of apitegromab.”
DiscussionFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary endpoint is change in lean body mass measured by DEXA, which is a surrogate for clinical outcomes such as physical function or health. Although the paper shows target engagement via increased latent myostatin levels, it does not cite validated evidence linking lean mass preservation to improved clinical outcomes in this context.
“Apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo.”
- INADEQUATEEffect sizeThe primary effect is a 1.9 kg difference in lean mass loss, which is a small fraction of total lean mass (baseline ~48-50 kg) and is not anchored to a minimal clinically important difference or functional benefit. The paper does not provide evidence that this magnitude of lean mass preservation translates to meaningful clinical outcomes.
“Apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo.”
Data authenticity concerns
1 finding · worst mediumAn 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.
- Other integrity concernAssessed
4 integrity concerns flagged (0 high).
- mediumotherTrial NCT06445075 was first submitted to ClinicalTrials.gov on 2024-05-22, after the registered study start date of 2024-05-21. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT06445075
reviewer’s wording - lowotherThe paper states 'No participants received semaglutide as a treatment assignment, due to a lack of drug availability at the time of EMBRAZE study initiation' - this is an odd statement since semaglutide was not part of the trial design; it may be a leftover from a protocol amendment.
“No participants received semaglutide as a treatment assignment, due to a lack of drug availability at the time of EMBRAZE study initiation”
MethodsFind in source - lowotherThe completer population (43 apitegromab, 44 placebo) is smaller than the randomized N (51 each), but the paper explains this is due to participants who completed treatment and had week 24 DEXA scans. This is expected.
“Efficacy analyses were based on the 43 participants receiving apitegromab and the 44 participants receiving placebo who completed treatment and had a week 24 dual-energy X-ray absorptiometry (DEXA) scan.”
Results ¶1Find in source
Reporting gaps
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction cites prior research on incretin mimetics and lean mass loss, and on myostatin biology and prior failed attempts at targeting myostatin, noting reasons such as off-target effects and suboptimal trial design. The rationale linking myostatin inhibition to lean mass preservation is logical and leads to the study objective. The paper also addresses limitations of prior research by highlighting the selective mechanism of apitegromab and appropriate trial design.
“Apitegromab is an investigational, fully human monoclonal antibody that selectively binds precursor forms of myostatin to potently inhibit myostatin activation, without activity toward other TGFβ superfamily members.”
“Collectively, these studies suggest that selective targeting of myostatin has therapeutic potential in preserving muscle as part of pharmacologic weight management.”
Randomization was 1:1 via an interactive web response system without blocking or stratification, and blinding was described (sponsor, participants, investigators, site personnel blinded except pharmacist). A power analysis is reported: assuming SD 4.6 kg, 43 per arm yields ~75% power to detect 2 kg difference. Inclusion/exclusion criteria are extensive and pre-specified. The completer population is defined for efficacy, and ITT analyses were repeated. Outlier handling is not explicitly described, but the completer population and ITT sensitivity analyses address missing data. Controls are appropriate (placebo plus tirzepatide). Independent replication is not applicable for a single pivotal phase 2 trial.
“Participants were randomized (1:1 via an interactive web response system managed by an independent vendor, without blocking or stratification factors)”
“The study sponsor, study participants, investigators and site personnel, with the exception of the pharmacist, were blinded to treatment assignments.”
“Assuming a standard deviation of 4.6 kg, an evaluable sample size of 43 participants per study arm was determined to yield approximately 75% power to detect an effect size of 2 kg for the primary endpoint of lean body mass change from baseline at week 24.”
“Participants were randomized (1:1 via an interactive web response system managed by an independent vendor, without blocking or stratification factors)”
“The study sponsor, study participants, investigators and site personnel, with the exception of the pharmacist, were blinded to treatment assignments.”
“Assuming a standard deviation of 4.6 kg, an evaluable sample size of 43 participants per study arm was determined to yield approximately 75% power to detect an effect size of 2 kg for the primary endpoint of lean body mass change from baseline at week 24.”
Table 1 reports sex (84.3% female in apitegromab, 80.4% in placebo), age (mean 44.2 and 42.6 years), weight, BMI, race, and other characteristics. Both sexes are included, so sex_justified is not applicable. Age, weight, and health status (BMI, comorbidities) are reported. Demographics are adequately reported. Species/strain and housing conditions are not applicable for a human trial.
“Most participants were women (apitegromab, 84.3% (43/51); placebo, 80.4% (41/51)), and mean age (s.d.) was similar (apitegromab, 44.2 years (11.0); placebo, 42.6 years (11.5)).”
“Female, n (%) | 43 (84.3) | 41 (80.4)”
“Weight, mean (s.d.) (kg) | 93.2 (14.9) | 98.8 (14.4)”
The Methods state: 'The trial protocol was approved by Advarra, a central institutional review board (IRB), as well as IRBs at participating sites and adhered to the Declaration of Helsinki and Good Clinical Practice guidelines.' This is a named ethics body with approval. Informed consent is mentioned: 'After a 4-week screening period and written informed consent...' Regulatory compliance is stated via Declaration of Helsinki and GCP. IACUC is not applicable for a human trial.
“The trial protocol was approved by Advarra, a central institutional review board (IRB), as well as IRBs at participating sites and adhered to the Declaration of Helsinki and Good Clinical Practice guidelines.”
“After a 4-week screening period and written informed consent, site personnel administered an initial dose of tirzepatide 2.5 mg plus apitegromab or placebo (day 1).”
“The trial protocol was approved by Advarra, a central institutional review board (IRB), as well as IRBs at participating sites”
“After a 4-week screening period and written informed consent”
“adhered to the Declaration of Helsinki and Good Clinical Practice guidelines”
Apitegromab is described as a fully human monoclonal antibody, and the dose (10 mg/kg every 4 weeks) is given. Tirzepatide is named with dose titration up to 15 mg weekly. DEXA scanners (Hologic and GE Lunar) are identified. Statistical software (SAS version 9.4) is identified. Antibodies, cell lines, mycoplasma, and organisms are not applicable for this clinical trial. Reagents are not applicable beyond the investigational products.
“Analyses were conducted using SAS version 9.4 software.”
“randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg −1 ) or tirzepatide plus placebo”
“Analyses were conducted using SAS version 9.4 software.”
The primary analysis uses a linear regression model controlling for baseline weight, baseline lean body mass, age, and sex. Two-sided p-values based on t-statistic are reported (e.g., P = 0.0014). Effect sizes with 80% CIs are reported throughout. Assumptions are not explicitly tested, but the use of a linear regression model with covariates is standard; for a clinical trial, this is adequate. Exact p-values are given for primary and secondary endpoints. Software is identified (SAS 9.4). Data presentation includes least square means with CIs and per-group n. Mathematical plausibility: I checked the AE percentages: 39/51 = 76.47% (reported 76%), 36/51 = 70.59% (reported 71%), 1/51 = 1.96% (reported 2%). These are consistent. The primary endpoint difference 1.9 kg with 80% CI (1.2-2.7) is plausible. No arithmetic errors detected.
“Least square means together with 80% CIs for each treatment group and the difference between groups in change from baseline at week 24 in lean body mass were estimated using a linear regression model controlling for baseline weight, baseline lean body mass, age and sex.”
“At week 24, apitegromab treatment significantly reduced lean mass loss, preserving 1.9 kg (1.2−2.7, least square means (80% confidence interval (CI))) of lean mass compared to placebo (nominal, P = 0.0014).”
“Change in lean mass (kg) (80% CI) (primary endpoint) | −1.6 (−2.3, −0.8) | −3.5 (−4.1, −2.8) | 1.9 (1.2, 2.7) | 0.0014”
“Least square means together with 80% CIs for each treatment group and the difference between groups in change from baseline at week 24 in lean body mass were estimated using a linear regression model controlling for baseline weight, baseline lean body mass, age and sex.”
“preserving 1.9 kg (1.2−2.7, least square means (80% confidence interval (CI))) of lean mass compared to placebo (nominal, P = 0.0014)”
“Change in lean mass (kg) (80% CI) (primary endpoint) | −1.6 (−2.3, −0.8) | −3.5 (−4.1, −2.8) | 1.9 (1.2, 2.7) | 0.0014”
The data availability statement says: 'Scholar Rock, Inc. is committed to sharing deidentified clinical trial data with external investigators upon reasonable request.' It provides an email and a process, but it is not a named managed-access platform like YODA or Vivli. It is more concrete than a bare 'on request' but lacks a formal mechanism. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is not mentioned; since the analysis used standard software (SAS), it may not be applicable, but the paper does not state this.
“Scholar Rock, Inc. is committed to sharing deidentified clinical trial data with external investigators upon reasonable request.”
“Scholar Rock, Inc. is committed to sharing deidentified clinical trial data with external investigators upon reasonable request.”
Trial registration is provided (NCT06445075). Methods are comprehensive. Limitations are discussed in the Discussion, including completer analysis, small sample, predominantly female, and lack of objective physical activity. Conclusions are proportional, noting proof-of-concept. Funding and competing interests are disclosed. A reporting guideline is not explicitly named, but the paper mentions a 'Reporting Summary' linked to the article, which is typical for Nature journals.
“ClinicalTrials.gov identifier: NCT06445075”
“Several limitations should be considered when interpreting these results. The primary efficacy analysis is based on participants who completed the 24 weeks of treatment, although supportive analysis based on the intention-to-treat (ITT) population showed consistent findings.”
“This work was supported by Scholar Rock, Inc. The funders had a role in the design and conduct of the trial; collection, management and analysis of the data; and the review of the manuscript.”
“ClinicalTrials.gov identifier: NCT06445075”
“Several limitations should be considered when interpreting these results.”
“This work was supported by Scholar Rock, Inc.”
Registered (3 IDs: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None foundReferences 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 20 references by DOI: 19 verified — 1 no DOI (shown, not verified).
- NO DOIMounjaro (tirzepatide). Package insert.No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
3 data/code links checked; 3 live.
- datahttp://clinicaltrials.gov/study/NCT06445075LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttp://clinicaltrials.gov/study/NCT03921528LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttp://clinicaltrials.gov/study/NCT05156320LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly consistency, clarity, punctuation.
- MINORconsistencyAbstract“least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001)”→ Use 'least squares mean' consistently (elsewhere it is 'least square mean').Minor terminology inconsistency.
- MINORclarityResults, Efficacy“preserving 1.9 kg (1.2−2.7, least square means (80% confidence interval (CI))) of lean mass compared to placebo (nominal, P = 0.0014)”→ Rephrase to 'preserving 1.9 kg (80% CI 1.2–2.7) of lean mass compared with placebo (nominal P = 0.0014)' for clarity.Awkward phrasing.
- MINORpunctuationTable 3“Any AE grade c ≥3”→ Ensure footnote 'c' is defined; it appears to be missing.Footnote marker may be missing.
- MINORconsistencyAbstract“least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo ( P = 0.001)”→ Ensure consistent use of 'least square mean' vs 'least squares mean' throughout.Minor terminology inconsistency.
- MINORclarityResults, Efficacy“preserving 1.9 kg (1.2−2.7, least square means (80% confidence interval (CI))) of lean mass compared to placebo (nominal, P = 0.0014)”→ Rephrase for clarity: 'apitegromab preserved 1.9 kg (80% CI 1.2–2.7) more lean mass than placebo (nominal P = 0.0014)'.Awkward phrasing.
- MINORpunctuationTable 3“Risk difference, apitegromab − placebo, % (95% CI)”→ Use en dash consistently for ranges and minus signs.Minor formatting.
The published work is robust and generally trustworthy, but an informed reader should weigh the retrospective registration (NCT06445075 submitted after study start), the vague data availability mechanism, and the minor internal inconsistency in the primary p-value (0.001 vs 0.0014). These do not invalidate the findings but warrant clarification or a correction.
- 1.HIGHreportingIn the Data availability section, specify a managed-access platform (e.g., Vivli or YODA) or a detailed data-sharing agreement process with a timeline for approval, to move from 'reasonable request' to a concrete mechanism.The current statement is vague and does not meet the standard for a concrete data-sharing mechanism, which is a common reviewer concern.
- 2.HIGHreportingIn the Methods or Reporting Summary, explicitly name the reporting guideline followed (e.g., CONSORT) and consider adding a CONSORT flow diagram.Explicitly naming the reporting guideline strengthens transparency and is expected for clinical trials.
- 3.HIGHstatisticsIn the Statistical analysis section, add a statement on how outliers were handled and whether model assumptions (e.g., linearity, normality of residuals) were checked.Both reviewers flagged outlier handling and assumptions as reported_but_inadequate; addressing these improves statistical rigor.
- 4.MEDIUMreportingReconcile the primary endpoint p-value in the Abstract (P = 0.001) with the Results/Table 2 (P = 0.0014) to ensure consistency.The integrity check flagged this internal contradiction; it is a minor rounding issue but should be corrected for accuracy.
- 5.MEDIUMreportingIn the Methods, clarify the statement about semaglutide not being administered due to lack of drug availability, as semaglutide was not part of the trial design.The integrity check noted this odd statement may be a leftover from a protocol amendment; clarifying avoids confusion.
- 6.MEDIUMdata codeAdd a statement about code availability, even if it is 'not applicable' because standard software was used.The code_sharing sub-criterion is not reported; a brief statement addresses this gap.
- 7.MEDIUMreportingIn the Discussion, expand on the unconventional use of 80% CIs and the 0.20 significance level, and their implications for interpretability.Reviewer 2 suggested this; it helps readers understand the statistical choices.
- 8.LOWcopyeditUse 'least squares mean' consistently throughout the manuscript (Abstract and Results).The copyedit pass flagged inconsistent terminology between 'least square mean' and 'least squares mean'.
- 9.LOWcopyeditRephrase the primary endpoint sentence in Results for clarity: 'apitegromab preserved 1.9 kg (80% CI 1.2–2.7) more lean mass than placebo (nominal P = 0.0014)'.The current phrasing is awkward and could be clearer.
- 10.LOWcopyeditIn Table 3, ensure footnote 'c' is defined and use en dashes consistently for ranges and minus signs.The copyedit pass flagged a missing footnote marker and inconsistent dash usage.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.