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Kaimen Rigor review

Prevention of type 2 diabetes through prediabetes remission without weight loss.

Sandforth A, Arreola EV, Hanson RL, Wewer Albrechtsen NJ, Holst JJ, Ahrends R, Coman C, Gerst F, Lorza-Gil E, Cheng Y, Sandforth L, Katzenstein S, Ganslmeier M, Seissler J, Hauner H, Perakakis N, Wagner R, Machann J, Schick F, Peter A, Lehmann R, Weigert C, Maurer J, Preissl H, Heni M, Szendrödi J, Kopf S, Solimena M, Schwarz P, Blüher M, Häring HU, Hrabé de Angelis M, Schürmann A, Kabisch S, Mai K, Pfeiffer AFH, Bornstein S, Stumvoll M, Roden M, Stefan N, Fritsche A, Birkenfeld AL, Jumpertz von Schwartzenberg R

DOI: 10.1038/s41591-025-03944-9
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-22

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/f41be13b-3676-41b5-808c-b3f7c5de37aa is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.25 / 5

Weak — serious problems found

Observational Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
CitationsUnresolved reference ×2−0.5★
ReportingStudy design partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 2 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is that prediabetes remission without weight loss reduces the risk of developing type 2 diabetes. The primary endpoint is the incidence of type 2 diabetes, which is a hard clinical outcome. However, the paper also relies on surrogate markers such as glucose regulation, insulin sensitivity, and body fat distribution to define remission and explain the mechanism. The claim of protection from T2D is based on the surrogate of achieving normal glucose regulation (NGR), and while the paper shows a reduction in T2D incidence, the primary basis for the efficacy claim is the achievement of NGR, which is a surrogate for long-term clinical benefit. The paper does not provide direct evidence that NGR itself is a validated surrogate for T2D prevention beyond the observed risk reduction, but the risk reduction is directly measured. The surrogate is the achievement of NGR, and the paper does not explicitly cite validated evidence linking NGR to reduced T2D risk beyond the study's own findings. However, the paper does show a direct reduction in T2D incidence, which is a hard outcome. The issue is that the primary claim is about remission (NGR) as a preventive measure, and the surrogate is the NGR status itself. The paper does not show target engagement for a drug, but for a lifestyle intervention. The surrogate is the glycemic status, and the paper does not provide a validated link between NGR and T2D prevention beyond the observed risk reduction. Therefore, the surrogate is inadequate because the efficacy claim rests on a surrogate (NGR) without a validated link to the clinical outcome, even though the clinical outcome is also measured. The paper's primary claim is that achieving NGR (a surrogate) prevents T2D, and while they show a risk reduction, the surrogate itself is not validated as a surrogate for T2D prevention in the context of this intervention.
“prediabetes remission is achievable without weight loss or even weight gain, and that it also protects against incident T2D”
Find in source
02Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
Trial NCT01947595 was first submitted to ClinicalTrials.gov on 2013-06-25, after the registered study start date of 2012-03. 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.
NCT01947595
reviewer’s wording

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 105AvailabilityBroken references and links 06Copyedit6 minor suggestions

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

The paper is a well-conducted post hoc analysis of a randomized trial with a validation cohort, reporting transparently on methods, ethics, and data availability. The main weakness is the lack of a priori powering and pre-specification for the subgroup analysis, which is acknowledged. Minor reporting issues include some threshold p-values and a few copyedit errors.

This is an observational post hoc analysis of a randomized trial; randomization and blinding are not applicable to the subgroup comparison. The statistics verification covered only 1 test (a subset of reported tests), so the absence of detected errors does not confirm overall statistical correctness. The citation check flagged 2 references not found in registries, which are addressed in the action items.

Numerical inconsistencies

1 finding · worst low

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

Internal contradictions in the reported numbersAssessed

Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .020 · recomputed p = .036Reviewer 1
RR reduction for T2D in PLIS responders vs nonresponders
“leading to a relative risk (RR) reduction of 71% in R over the period of up to 10 years (RR = 0.29, 95% CI = 0.09–0.91, P = 0.02; Fig. )”
Find in source
Taken as given: The RR is 0.29 with 95% CI 0.09-0.91.; The CI is two-sided at 95%.; The p-value is for the RR being different from 1.
Method: Recomputed p-value from RR and 95% CI using the pCI function for a ratio.
How we recomputed it: pCI(0.29, 0.09, 0.91, 1)

lowinternal contradiction
The abstract states 'up to 10 years' follow-up, while the methods state 'mean of 5.2 ± 2.8 years (max = 9.9 years)' and results mention 'up to 10 years'. This is a minor inconsistency in the maximum follow-up duration.
protects from T2D development for up to 10 years after the LI started (Abstract) vs. Volunteers participated in this study for a mean of 5.2 ± 2.8 years (max = 9.9 years) (Methods)
Abstractreviewer’s wording
lowinternal contradiction
The number of responders in PLIS is reported as 51, but in the DPP replication, the number of responders is 25, and the total non-weight-loss group is 494, which seems plausible but the ratio differs.
Of these, 51 returned to NGR... (PLIS); We also identified 494 individuals who did not lose or even gain body weight... (DPP)
Resultsreviewer’s wording

Overstated conclusions

2 findings · worst high

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

Efficacy rests on an unvalidated surrogate endpointAssessed
Conclusions only partially backed by the presented evidenceAssessed

10 major claims checked against the paper's own evidence: 2 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

partialReviewer 1
The underlying mechanisms include improved β-cell-GLP-1 sensitivity.
The paper shows improved β-cell-GLP-1 sensitivity in R, but this is based on calculated indices and not direct measurements, and the evidence is indirect.
Evidence: Extended Data Fig. 5 shows β-cell incretin sensitivity improved in R, P=0.0050.
“these calculations display that β-cell-GLP-1 sensitivity exhibited marked improvements in R, but not in NR”
ResultsFind in source
partialReviewer 2
Glycemic targets should be included in clinical practice guidelines for T2D prevention.
The data support the benefit of remission, but the recommendation to change guidelines is an extrapolation.
Evidence: The study shows remission reduces T2D risk, but does not directly test guideline changes.
we recommend achieving metabolic health by incorporating glycemic targets to reach NGR (prediabetes remission) in addition to weight loss.
Discussionreviewer’s wording
supportedReviewers 1, 2
Prediabetes remission without weight loss is achievable and protects against incident T2D.
The paper provides direct evidence from PLIS and DPP showing that responders had a 71% and 73% RR reduction in T2D, respectively.
Evidence: Kaplan-Meier curves, RR=0.29 (95% CI 0.09-0.91) in PLIS and RR=0.27 (95% CI 0.11-0.66) in DPP.
“demonstrating that prediabetes remission is achievable without weight loss or even weight gain, and that it also protects against incident T2D.”
AbstractFind in source
supportedReviewer 1
Non-weight-loss-induced remission is characterized by increased subcutaneous adipose tissue and decreased visceral adipose tissue compared to nonremission.
MRI data show SCAT increased more in R and VAT increased in NR, with significant group-by-time interactions.
Evidence: Fig. 3: SCAT P=0.035, VAT P=0.031, SCAT/VAT ratio P<0.0001.
“SCAT increased more in R versus NR (14.41 ± 2.39 l to 15.7 ± 2.06 l in R versus 14.97 ± 1.06 l to 14.66 ± 0.98 l in NR, P group over time = 0.035)”
ResultsFind in source
supportedReviewer 1
Non-weight-loss-induced remission is mediated by improved insulin sensitivity and insulin secretion.
OGIS and insulin secretion indices improved in R but not NR, with significant group-by-time interactions.
Evidence: Fig. 2: OGIS P=0.0035, C-peptide/glucose AUC P=0.043, Adaptation Index P=0.025.
“We found that throughout the LI, insulin sensitivity did not change in NR but increased in R.”
ResultsFind in source
supportedReviewer 1
The findings were reproduced in the US Diabetes Prevention Program.
DPP validation showed similar BMI changes, VAT changes, and improved insulin sensitivity/secretion in responders, with a 73% RR reduction.
Evidence: Extended Data Fig. 6 and 7, RR=0.27 (95% CI 0.11-0.66).
“These data reproduce the findings that prediabetes remission without weight loss is characterized by improved insulin sensitivity as well as improved insulin secretion”
ResultsFind in source
supportedReviewer 1
Weight gain was similar in responders and nonresponders, but adipose tissue was differentially redistributed.
BMI and body weight increased similarly in both groups, while fat distribution differed significantly.
Evidence: BMI P=0.24, weight P=0.45, but VAT and SCAT changes differed.
BMI increased similarly in both groups (29.6 ± 2.1 kg m −2 to 30.6 ± 2.1 kg m −2 in R versus 30.5 ± 0.8 kg m −2 to 31.3 ± 0.9 kg m −2 in NR, P group over time = 0.24)
Resultsreviewer’s wording
supportedReviewer 2
Non-weight-loss remission is characterized by increased subcutaneous adipose tissue and decreased visceral adipose tissue.
MRI data show SCAT increased more in responders while VAT increased in nonresponders.
Evidence: SCAT/VAT ratio increased in R, decreased in NR (P < 0.0001).
SCAT increased more in R versus NR... showing that with weight gain, R predominantly stored additional energy in SCAT but NR in VAT.
Resultsreviewer’s wording
supportedReviewer 2
Improved insulin sensitivity and β-cell function mediate non-weight-loss remission.
OGIS and insulin secretion indices improved in responders but not nonresponders.
Evidence: OGIS increased in R, unchanged in NR (P=0.0035); C-peptide/glucose AUC increased in R (P=0.043).
insulin sensitivity did not change in NR but increased in R... insulin secretion and β-cell function increased in R but not in NR.
Resultsreviewer’s wording
supportedReviewer 2
The findings are reproduced in the US Diabetes Prevention Program.
DPP replication shows similar improvements in insulin sensitivity and secretion and reduced T2D risk.
Evidence: DPP responders had improved insulin sensitivity and secretion, and RR reduction of 73%.
These data reproduce the findings that prediabetes remission without weight loss is characterized by improved insulin sensitivity as well as improved insulin secretion.
Resultsreviewer’s wording

Premise concern: surrogate not validated for clinical benefit.

INADEQUATESurrogate endpoint
The primary efficacy claim is that prediabetes remission without weight loss reduces the risk of developing type 2 diabetes. The primary endpoint is the incidence of type 2 diabetes, which is a hard clinical outcome. However, the paper also relies on surrogate markers such as glucose regulation, insulin sensitivity, and body fat distribution to define remission and explain the mechanism. The claim of protection from T2D is based on the surrogate of achieving normal glucose regulation (NGR), and while the paper shows a reduction in T2D incidence, the primary basis for the efficacy claim is the achievement of NGR, which is a surrogate for long-term clinical benefit. The paper does not provide direct evidence that NGR itself is a validated surrogate for T2D prevention beyond the observed risk reduction, but the risk reduction is directly measured. The surrogate is the achievement of NGR, and the paper does not explicitly cite validated evidence linking NGR to reduced T2D risk beyond the study's own findings. However, the paper does show a direct reduction in T2D incidence, which is a hard outcome. The issue is that the primary claim is about remission (NGR) as a preventive measure, and the surrogate is the NGR status itself. The paper does not show target engagement for a drug, but for a lifestyle intervention. The surrogate is the glycemic status, and the paper does not provide a validated link between NGR and T2D prevention beyond the observed risk reduction. Therefore, the surrogate is inadequate because the efficacy claim rests on a surrogate (NGR) without a validated link to the clinical outcome, even though the clinical outcome is also measured. The paper's primary claim is that achieving NGR (a surrogate) prevents T2D, and while they show a risk reduction, the surrogate itself is not validated as a surrogate for T2D prevention in the context of this intervention.
“prediabetes remission is achievable without weight loss or even weight gain, and that it also protects against incident T2D”
Find in source
ADEQUATEEffect size
The primary effect size is the relative risk reduction of 71% in responders compared to non-responders for developing type 2 diabetes over up to 10 years. This is a large and clinically meaningful effect, and it is statistically supported (RR = 0.29, 95% CI = 0.09–0.91, P = 0.02). The effect is anchored to the clinical outcome of T2D incidence, which is a hard endpoint. Therefore, the effect size is adequate.
“relative risk (RR) reduction of 71% in R over the period of up to 10 years (RR = 0.29, 95% CI = 0.09–0.91, P = 0.02)”
Find in source

Data authenticity concerns

1 finding · worst medium

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

Other integrity concernAssessed

3 integrity concerns flagged (0 high).

mediumother
Trial NCT01947595 was first submitted to ClinicalTrials.gov on 2013-06-25, after the registered study start date of 2012-03. 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.
NCT01947595
reviewer’s wording

Reporting gaps

1 finding · worst medium

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

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

Eight Dimensions7 pass · 1 warn

The introduction cites prior studies (DPPOS, PLIS, DIRECT) and identifies a gap: neither DIRECT nor DPP reported on preventive outcomes in patients who achieved remission without weight loss. The rationale is coherent, and the study aims to fill this gap. Limitations of prior work are implicitly addressed by focusing on a novel subgroup.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on prediabetes remission and weight loss, and logically links it to the study's objectives.

Evidence

paraphrase[Introduction, paragraph 2]

“The U.S. Diabetes Prevention Program (DPP) Outcome Study (DPPOS) has demonstrated that reversal of impaired glucose regulation to normal at least once during a lifestyle intervention (LI) was effective in reducing the risk of T2D and microvascular disease.”

“However, neither DIRECT nor DPP reported on the preventive outcomes of patients who did not reduce body weight but achieved remission.”

Introduction ¶3Find in source

“Here, we provide evidence that non-weight-loss-induced remission of prediabetes protects from T2D development for up to 10 years after the LI started, and that it is characterized by increased subcutaneous adipose tissue (SCAT) compared to nonremission, where VAT increases.”

Introduction ¶3Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior work on prediabetes remission and weight loss, and logically links it to the study objectives.

Evidence

paraphrase[Introduction, paragraph 2]

“However, neither DIRECT nor DPP reported on the preventive outcomes of patients who did not reduce body weight but achieved remission.”

Introduction ¶3Find in source

paraphrase[Introduction, paragraph 3]

“Here, we provide evidence that non-weight-loss-induced remission of prediabetes protects from T2D development for up to 10 years after the LI started.”

The parent trial PLIS was randomized, but this post hoc analysis does not describe randomization methods or blinding for the subgroup analysis. Inclusion/exclusion criteria are clearly defined (no weight loss over 12 months). Power analysis is not reported, and the authors acknowledge the lack of a priori powering. Outlier handling is not explicitly described, but missing data imputation is mentioned. Controls are not applicable as this is an observational comparison of responders vs nonresponders.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsNOT REPORTED

outlier handlingINADEQUATE

randomization unitNOT REPORTED

inclusion exclusionADEQUATE

randomization methodNOT REPORTED

replicate distinctionN/A

independent replicationADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

The study design is a post hoc analysis of a randomized trial, but randomization and blinding are not applicable to the subgroup analysis; power analysis is lacking, and inclusion/exclusion criteria are described but not pre-specified for this analysis.

Evidence

“This study is additionally limited by the lack of a priori powering due to the post hoc nature of this analysis.”

LimitationsFind in source

“For this analysis, individuals from PLIS who did not experience weight loss over the 12-month period of those of the intensified LI, the conventional LI or the control intervention were included.”

MethodsFind in source

“To exclude any potential effect that may be specific to our cohort and to enhance the generalizability of the results, we validated our findings in repository data from DPP.”

ResultsFind in source

WARNReviewer 2· 85% conf

The study design is a post hoc analysis of a randomized trial, with clear inclusion/exclusion criteria and statistical methods, but lacks a priori power analysis and detailed randomization/blinding information.

Evidence

MethodsFind in source

“This study is additionally limited by the lack of a priori powering due to the post hoc nature of this analysis.”

Discussion ¶10Find in source

“We also identified 494 individuals who did not lose or even gain body weight after 12 months of the intervention.”

ResultsFind in source

Sex is reported for both groups, with percentages given. Age is reported as median with standard deviation. Health status is implied by prediabetes criteria. Demographics include sex and age, but race/ethnicity and comorbidities are not detailed. Species/strain and housing conditions are not applicable as this is a human study.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Biological variables are well reported: sex, age, and health status are described; demographics are provided; species/strain and housing are not applicable as this is a human study.

Evidence

“Overall, there were more women in both groups and R tended to have more women than NR (60.1% in NR versus 74.5% in R, P = 0.085).”

ResultsFind in source

“R were younger (median = 54.4 ± 17.6 years) than NR (59.4 ± 15.5 years, P = 0.013)”

ResultsFind in source

“Baseline characteristics for both groups are given in Extended Data Table .”

ResultsFind in source

PASSReviewer 2· 90% conf

Biological variables such as sex, age, and health status are reported, and demographics are provided for the study population.

Evidence

“Overall, there were more women in both groups and R tended to have more women than NR (60.1% in NR versus 74.5% in R, P = 0.085).”

ResultsFind in source

“R were younger (median = 54.4 ± 17.6 years) than NR (59.4 ± 15.5 years, P = 0.013)”

ResultsFind in source

absence[Extended Data Table 1]

Demographics are limited to sex and age; race/ethnicity and comorbidities are not reported.

PLIS has ethics approval from the ethics committee of the University Clinic of Tübingen with protocol number, and written informed consent was obtained. DPP has ethics approval from each participating center's IRB and written informed consent. Regulatory compliance is implied by adherence to ethical standards.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethical approvals are adequately reported for both PLIS and DPP, including named ethics committees and informed consent.

Evidence

“approved by the ethics committee of the University Clinic of Tübingen (Tübingen, 55/2012; ClinicalTrials.gov registration: NCT01947595”

MethodsFind in source

“Written informed consent was provided by each participant at inclusion.”

MethodsFind in source

“Ethics approval for the study was provided by the institutional review board of each participating clinical center. Written informed consent was obtained from all DPP participants.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethical approvals and informed consent are clearly documented for both PLIS and DPP cohorts.

Evidence

“approved by the ethics committee of the University Clinic of Tübingen (Tübingen, 55/2012; ClinicalTrials.gov registration: NCT01947595”

MethodsFind in source

“Written informed consent was provided by each participant at inclusion.”

MethodsFind in source

“Ethics approval for the study was provided by the institutional review board of each participating clinical center. Written informed consent was obtained from all DPP participants.”

MethodsFind in source

The study uses ELISA kits (e.g., adiponectin from ALPCO) and immunoassays for incretins, which are identified. Software tools (R, RStudio, PLINK) are named with versions. Genotyping chips are specified. However, catalog numbers for some reagents are not provided, and antibody validation is not detailed.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Key resources are adequately identified: the lifestyle intervention is described, assay kits and software are named, and the DPP data source is specified.

Evidence

“nectin (80-ADPHU-E01; ALPCO) were determined using ELISA”

MethodsFind in source

“Statistical analyses were performed using RStudio (version 2024.12.0 + 467) with R (version 4.4.1).”

Statistical analysisFind in source

“Quality control was performed on all participants using the PLINK 1.9 software.”

MethodsFind in source

PASSReviewer 2· 85% conf

Key resources such as assay kits, software, and genetic data are identified, though some reagent details are incomplete.

Evidence

“nectin (80-ADPHU-E01; ALPCO) were determined using ELISA”

MethodsFind in source

“Statistical analyses were performed using RStudio (version 2024.12.0 + 467) with R (version 4.4.1).”

Statistical analysisFind in source

“Individuals from PLIS were genotyped onto two different versions of the Illumina Global Screening Array chip (280 on GSA-MD-24v1 and 549 on GSA-MD-24v2).”

MethodsFind in source

Tests are named (linear mixed effects models, Wilcoxon rank-sum, Fisher's exact, log-rank). Assumptions are addressed via diagnostic plots. Exact p-values are reported throughout. Effect sizes with 95% CIs are provided in Extended Data Fig. 9. Software is identified. Data presentation includes individual data points in figures and per-group n. Mathematical plausibility is not applicable for most continuous outcomes due to large N and model-derived statistics.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical methods are well described, including mixed effects models, exact p-values, effect sizes with CIs, and software identification. Mathematical plausibility checks were not possible for most continuous outcomes.

Evidence

“Linear mixed effects models with group (that is, R and NR), time point and the interaction group × time point as model terms adjusted for age, sex, BMI, risk stratification and intervention intensity as fixed effects and each individual as random effect were fitted to analyze longitudinal data.”

Statistical analysisFind in source

“P group over time: 0.0035”

ResultsFind in source

“To avoid overreliance on significance testing and dichotomization, we report β coefficients for all models, including 95% confidence intervals in Extended Data Fig. .”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

Statistical methods are well-described, with named tests, effect sizes with CIs, and software identified; however, exact p-values are not always reported.

Evidence

Statistical analysisFind in source

“To avoid overreliance on significance testing and dichotomization, we report β coefficients for all models, including 95% confidence intervals in Extended Data Fig.”

Statistical analysisFind in source

“P group over time < 0.0001”

ResultsFind in source

PLIS data are not publicly accessible but can be requested via a data steering committee with a formal data use agreement and a response timeframe (3 months). DPP data are available through the NIDDK Central Repository. No custom code was generated, so code sharing is not applicable.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability is adequately described with a concrete access route for PLIS data and a repository for DPP data; code availability is stated as no custom code.

Evidence

“The datasets from this study are not publicly accessible due to national data protection regulations and ethical restrictions designed to protect participant privacy. They can be requested after publication by contacting the corresponding author. Each request will be reviewed by the PLIS data steering committee, and approved access will require a formal data use agreement. The PLIS data steering committee will respond to requests within 3 months.”

Data availabilityFind in source

“Data from the DPP referenced in this study can be obtained through the U.S. NIDDK Central Repository ( https://repository.niddk.nih.gov/ ) .”

Data availabilityFind in source

“No custom code was generated for this study.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability is clearly stated with a managed access mechanism, and code availability is addressed.

Evidence

“They can be requested after publication by contacting the corresponding author. Each request will be reviewed by the PLIS data steering committee, and approved access will require a formal data use agreement.”

Data availabilityFind in source

“Data from the DPP referenced in this study can be obtained through the U.S. NIDDK Central Repository ( https://repository.niddk.nih.gov/ )”

Data availabilityFind in source

“No custom code was generated for this study.”

Data availabilityFind in source

Methods are comprehensive. The trial is registered (NCT01947595). A reporting guideline is not explicitly mentioned, but the paper includes a reporting summary. All outcomes are reported, including null results. Limitations are discussed in detail. Conclusions are proportional, acknowledging the post hoc nature. Funding and competing interests are disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

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

Evidence

“ClinicalTrials.gov registration: NCT01947595”

MethodsFind in source

“This study is limited by the surrogate parameters derived from the OGTT for estimation of insulin sensitivity and secretion/β-cell function.”

LimitationsFind in source

paraphrase[Acknowledgements and Competing interests]

“PLIS and this post hoc analysis were supported by the German Center for Diabetes Research... All other authors declare no competing interests.”

PASSReviewer 2· 85% conf

The manuscript is transparent about methods, limitations, and funding, and conclusions are proportional to the evidence.

Evidence

“ClinicalTrials.gov registration: NCT01947595”

MethodsFind in source

“This study is limited by the surrogate parameters derived from the OGTT for estimation of insulin sensitivity and secretion/β-cell function.”

Discussion ¶10Find in source

paraphrase[Acknowledgements and Competing interests]

“PLIS and this post hoc analysis were supported by the German Center for Diabetes Research... All other authors declare no competing interests.”

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

ClinicalTrials.gov

NCT01947595

Broken references and links

1 finding · worst low

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

References not resolvable to a published paperRecomputed

Checked 99 references by DOI: 1 verified — 2 DOI unresolved, 96 no DOI (shown, not verified).

UNRESOLVED10.1016/s0140-6736(24
Prediabetes remission and cardiovascular morbidity and mortality: a post-hoc analysis from DPPOS and DaQingDPOS
Cited DOI does not resolve to any Crossref record.
UNRESOLVED10.58020/3hw5-cf91
Diabetes Prevention Program (DPP) (version 9)
Cited DOI does not resolve to any Crossref record.
NO DOI
Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Incident type 2 diabetes attributable to suboptimal diet in 184 countries
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prediabetes remission to reduce the global burden of type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prediabetes: a high-risk state for diabetes development
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prediabetes and the risk of cancer: a meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
2. Classification and diagnosis of diabetes: standards of care in diabetes-2023
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prevention or delay of diabetes and associated comorbidities: standards of care in diabetes-2025
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Regression from prediabetes to normal glucose regulation and prevalence of microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Different effects of lifestyle intervention in high- and low-risk prediabetes: results of the randomized controlled Prediabetes Lifestyle Intervention Study (PLIS)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prediabetes remission for type 2 diabetes mellitus prevention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The anti-inflammatory effect of exercise
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Time course of normalization of functional β-cell capacity in the diabetes remission clinical trial after weight loss in type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Lower hepatic fat is associated with improved insulin secretion in a high-risk prediabetes subphenotype during lifestyle intervention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham Heart Study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Obesity is associated with increased basal and postprandial β-cell insulin secretion even in the absence of insulin resistance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Estimation of insulin secretion rates from C-peptide levels: comparison of individual and standard kinetic parameters for C-peptide clearance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
International diabetes federation position statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Obesity treatment: weight loss versus increasing fitness and physical activity for reducing health risks
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Exercise-induced reduction in obesity and insulin resistance in women: a randomized controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Subclassification of obesity for precision prediction of cardiometabolic diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Definition and diagnostic criteria of clinical obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A new framework for the diagnosis, staging and management of obesity in adults
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Exercise training remodels subcutaneous adipose tissue in adults with obesity even without weight loss
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Long-term exercise training has positive effects on adipose tissue in overweight or obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of the volume and intensity of exercise training on insulin sensitivity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Multi-ancestry polygenic mechanisms of type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genetic basis of early onset and progression of type 2 diabetes in South Asians
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Association of genetic variants related to gluteofemoral vs abdominal fat distribution with type 2 diabetes, coronary disease, and cardiovascular risk factors
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients [corrected]
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Thiazolidinediones improve β-cell function in type 2 diabetic patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Insulin-sensitive obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Expression of mesenchymal and α-cell phenotypic markers in Islet β-cells in recently diagnosed diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with type 2 (non-insulin-dependent) diabetes mellitus
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Glucagonostatic potency of GLP-1 in patients with type 2 diabetes, patients with type 1 diabetes, and healthy control subjects
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Alterations in glucagon levels and the glucagon-to-insulin ratio in response to high dietary fat or protein intake in healthy lean adult twins: a post hoc analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Role of weight loss-induced prediabetes remission in the prevention of type 2 diabetes: time to improve diabetes prevention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of semaglutide on regression and progression of glycemia in people with overweight or obesity but without diabetes in the SELECT trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effect of thiazolidinediones on adiponectin serum level: a meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Prediabetes Remission and Cardiovascular Morbidity and Mortality: A post-hoc analysis from the Diabetes Prevention Program Outcome Study and the DaQing Diabetes Prevention Outcome Study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Addressing weight loss recidivism: a clinical focus on metabolic rate and the psychological aspects of obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Probability of an obese person attaining normal body weight: cohort study using electronic health records
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Subphenotype-dependent benefits of bariatric surgery for individuals at risk for type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Reproducibility of a prediabetes classification in a contemporary population
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Regression from prediabetes to normal glucose levels is more frequent than progression towards diabetes: the CRONICAS cohort study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Precision medicine in people at risk for diabetes and atherosclerotic cardiovascular disease: a fresh perspective on prevention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A short questionnaire for the measurement of habitual physical activity in epidemiological studies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A model-based method for assessing insulin sensitivity from the oral glucose tolerance test
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Improved quantification of muscle insulin sensitivity using oral glucose tolerance test data: the MISI calculator
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Insulinogenic indices from insulin and C-peptide: comparison of β-cell function from OGTT and IVGTT
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Improved meal-related β-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The measurement of insulin clearance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The use of areas under curves in diabetes research
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Older subjects with β-cell dysfunction have an accentuated incretin release
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Fat distribution patterns and future type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Follow-up whole-body assessment of adipose tissue compartments during a lifestyle intervention in a large cohort at increased risk for type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Topography mapping of whole body adipose tissue using a fully automated and standardized procedure
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Fat quantification with IDEAL gradient echo imaging: correction of bias from T(1) and noise
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point Dixon and three-point IDEAL
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Hepatic lipid accumulation in healthy subjects: a comparative study using spectral fat-selective MRI and volume-localized 1H-MR spectroscopy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A rapid method of total lipid extraction and purification
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Simultaneous metabolite, protein, lipid extraction (SIMPLEX): a combinatorial multimolecular omics approach for systems biology
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
LipidXplorer: a software for consensual cross-platform lipidomics
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome in human plasma, using the Luminex-100 system
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Preanalytical impact on the accuracy of measurements of glucagon, GLP-1 and GIP in clinical trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The NHGRI–EBI GWAS catalog: knowledgebase and deposition resource
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

2 data/code links checked; 2 live.

datahttps://repository.niddk.nih.gov/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://repository.niddk.nih.gov/study/38LIVEHTTP 200
Resolved page looks like data.

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

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

MINORtypoExtended Data Fig. 4 title
“livestyle”
→ lifestyle
Typo in figure title.
MINORconsistencyResults, Body fat distribution
“P group over time < 0.0001”
→ P group over time < 0.0001 (consistent formatting)
Inconsistent use of spaces around '<' in p-values.
MINORclarityMethods, Statistical analysis
“To avoid overreliance on significance testing and dichotomization, we report β coefficients for all models, including 95% confidence intervals in Extended Data Fig. .”
→ Specify which Extended Data Figure contains the β coefficients.
The sentence ends with 'Extended Data Fig. .' missing the figure number.
MINORtypoAbstract
“subcutaneous deposits”
→ subcutaneous depots
Inconsistent terminology; 'deposits' vs 'depots' used elsewhere.
MINORconsistencyResults, Body fat distribution
“SCAT/VAT ratio”
→ SCAT/VAT ratio
Ensure consistent use of 'SCAT' and 'VAT' abbreviations throughout.
MINORgrammarMethods, Statistical analysis
“To avoid overreliance on significance testing and dichotomization, we report β coefficients for all models, including 95% confidence intervals in Extended Data Fig.”
→ To avoid overreliance on significance testing and dichotomization, we report β coefficients for all models, including 95% confidence intervals, in Extended Data Fig.
Missing comma before 'in Extended Data Fig.'

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust in its reporting and methodology, but readers should weigh the post hoc nature, lack of a priori powering, and the retrospective registration of the parent trial. The minor internal inconsistencies (follow-up duration, responder counts) and the two unresolved references warrant attention, possibly through an erratum or clarification.

1.
HIGHreporting
In the Methods, specify the exact Extended Data Figure number for the β coefficients and 95% confidence intervals (currently 'Extended Data Fig. .').
The missing figure number is a copyedit error that undermines reproducibility.
2.
HIGHreporting
In the Abstract and Results, reconcile the follow-up duration: state the maximum follow-up as 9.9 years (or clarify the 'up to 10 years' claim) to resolve the internal contradiction.
The inconsistency between 'up to 10 years' and 'max = 9.9 years' could confuse readers and is a validity concern.
3.
HIGHreporting
In the Results, clarify the number of responders in the DPP replication (25) relative to the total non-weight-loss group (494) and ensure the ratio is accurately described.
The differing responder counts between cohorts may raise questions about the comparability of the validation.
4.
HIGHreporting
Verify and correct the two references not found in registries: 'Prediabetes remission and cardiovascular morbidity and mortality: a post-hoc analysis from DPPOS and DaQingDPOS' (DOI 10.1016/s0140-6736(24) and 'Diabetes Prevention Program (DPP) (version 9)' (DOI 10.58020/3hw5-cf91).
Unresolved references may indicate fabrication or citation errors; they must be corrected or removed.
5.
MEDIUMreporting
In the Methods, add a statement on whether the study followed a specific reporting guideline (e.g., STROBE) for observational studies.
Explicitly naming a reporting guideline enhances transparency and reproducibility.
6.
MEDIUMstatistics
In the Results, provide exact p-values for comparisons reported as thresholds (e.g., 'P < 0.0001') where possible.
Exact p-values improve transparency and allow readers to assess the strength of evidence.
7.
MEDIUMrigor
In the Discussion, explicitly address the potential for residual confounding due to the post hoc stratification and the lack of a priori powering.
Acknowledging these limitations helps readers interpret the findings appropriately.
8.
MEDIUMdata code
In the Data Availability section, consider depositing de-identified aggregate data or analysis scripts in a public repository to enhance reproducibility.
While individual-level data cannot be shared, aggregate data or scripts would increase transparency.
9.
MEDIUMreporting
In the Methods, describe how outliers were handled in the statistical analysis, or explicitly state that no outliers were excluded.
Outlier handling is a key methodological detail that is currently missing.
10.
MEDIUMreporting
In the Methods, clarify the handling of missing data for the DPP cohort, as imputation was only mentioned for PLIS.
Consistent reporting of missing data handling across cohorts is necessary for reproducibility.
11.
LOWcopyedit
Fix the typo 'livestyle' to 'lifestyle' in the Extended Data Fig. 4 title.
Correcting typos improves the professional quality of the manuscript.
12.
LOWcopyedit
Standardize the use of 'subcutaneous deposits' vs 'subcutaneous depots' in the Abstract and Results.
Consistent terminology avoids confusion.
13.
LOWcopyedit
Ensure consistent formatting of p-values (e.g., spaces around '<') throughout the Results.
Consistent formatting improves readability.
14.
LOWreporting
In the Methods, add a note about the retrospective registration of the parent trial (NCT01947595) and its implications.
Transparency about registration timing is important for assessing the risk of selective reporting.

Full text (79,881 chars · analyzed ~94%, head + tail)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

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.”

How stars are deducted

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.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

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.

Prevention of type 2 diabetes through prediabetes remission without weight loss.

DOI

10.1038/s41591-025-03944-9

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-22