Alpha¹ by KaimenConfidential

Kaimen Rigor review

Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.

Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, Lincoff AM, McGuire DK, Miller D, Nauck MA, Nishiyama H, Nissen SE, Sattar N, Weerakkody G, Wiese RJ, Zinman B, Zoungas S, Basile J, Davies MJ, Giorgino F, Kellerer M, Ji L, Varkonyi T, Menon V, Broder JC, Herschtal A, D'Alessio D, SURPASS-CVOT Investigators

DOI: 10.1056/NEJMoa2505928
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-20

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/954a5a22-33bf-44f2-b17a-31788c48dfe1 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ReportingData & code availability 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: 22 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.
No data or code availability links were detected to verify.

Findings by category

101ArithmeticNumerical inconsistencies 02OverreachNone found 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit2 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.

This is a well-conducted and well-reported randomized controlled trial with strong methodological rigor across most dimensions. The primary weakness is the vague data availability statement, which does not specify the access mechanism or repository.

Both reviewers agreed on study type (interventional). All eight dimensions were applicable; no dimensions were excluded as not applicable. The reviewers' assessments were highly concordant, with minor divergence on the regulatory compliance sub-criterion within ethical approvals, which did not affect the overall status.

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 = .090 · recomputed p = .096Reviewer 1
Verify the p-value for superiority of the primary endpoint (HR=0.92, 95.3% CI 0.83-1.01). The paper reports P=0.09 for superiority. The p-value for superiority can be approximated from the hazard ratio and its confidence interval using the pCI function, assuming the CI is a 95.3% CI (which corresponds to a two-sided alpha of 0.047). However, the pCI function assumes a 95% CI. To adjust, we can compute the p-value from the z-score derived from the CI. The z-score for a 95.3% CI is approximately 1.98. The p-value for HR=0.92 with CI 0.83-1.01 is approximately 0.09. We can use pCI(0.92, 0.83, 1.01, 1) which assumes 95% CI, giving a p-value close to 0.09. The reported p is 0.09, so this is consistent.
“hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority”
Find in source
Taken as given: The hazard ratio is 0.92 and the 95.3% CI is 0.83 to 1.01.; The pCI function uses a normal approximation for the log hazard ratio.; The reported p-value for superiority is two-sided.
Method: Used pCI to compute the two-sided p-value from the hazard ratio and its confidence interval, assuming a log-normal distribution.
How we recomputed it: pCI(0.92, 0.83, 1.01, 1)

lowinternal contradiction
The abstract states 'A total of 13,299 patients underwent randomization; 134 were subsequently excluded... The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group.' However, the Results section states '6648 were assigned to the tirzepatide group and 6651 to the dulaglutide group. A total of 134 patients (62 in the tirzepatide group and 72 in the dulaglutide group) discontinued... the 13,165 remaining patients were included in the modified intention-to-treat population (6586 in the tirzepatide group and 6579 in the dulaglutide group).' The numbers are consistent: 6648-62=6586 and 6651-72=6579. No contradiction.
A total of 13,299 patients underwent randomization; 134 were subsequently excluded... 6586 patients in the tirzepatide group and 6579 in the dulaglutide group.
Abstractreviewer’s wording

Overstated conclusions

None found

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.

Checked — nothing surfaced.

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

supportedReviewers 1, 2
Tirzepatide was noninferior to dulaglutide with respect to the primary composite endpoint.
The primary endpoint result (HR 0.92, 95.3% CI 0.83-1.01) has an upper bound below the prespecified noninferiority margin of 1.05, and the p-value for noninferiority is 0.003, supporting the claim.
Evidence: Primary endpoint: 801 events (12.2%) vs 862 (13.1%), HR 0.92, 95.3% CI 0.83-1.01, P=0.003 for noninferiority.
“tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke.”
AbstractFind in source
supportedReviewers 1, 2
The incidence of adverse events appeared to be similar in the two groups.
Table 3 shows similar rates of any adverse event (89.6% vs 88.7%) and serious adverse events (31.8% vs 31.9%), supporting the claim.
Evidence: Table 3: Any adverse event 5956 (89.6%) vs 5894 (88.7%); serious adverse event 2117 (31.8%) vs 2121 (31.9%).
The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group.
Abstractreviewer’s wording
supportedReviewer 1
Tirzepatide was associated with greater improvements in metabolic risk factors compared to dulaglutide.
The paper reports significant differences in HbA1c, body weight, triglycerides, and blood pressure, all favoring tirzepatide, with CIs excluding zero.
Evidence: HbA1c change -1.66 vs -0.88 percentage points (difference -0.78, 95% CI -0.84 to -0.72); body weight -11.6% vs -4.8% (difference -6.8, 95% CI -7.1 to -6.5).
The glycated hemoglobin level decreased to 6.73% (50 mmol per mole) in the tirzepatide group (change from baseline, −1.66 percentage points) and to 7.51% (59 mmol per mole) in the dulaglutide group (change from baseline, −0.88 percentage points), with a between-group difference of −0.78 percentage points (−9 mmol per mole; 95% CI, −0.84 to −0.72 [−9 to −8]).
Resultsreviewer’s wording
supportedReviewer 1
A prespecified secondary analysis suggested a possible lower incidence of death from any cause and noncardiovascular causes in the tirzepatide group.
The paper reports HR 0.84 (95% CI 0.75-0.94) for all-cause death and HR 0.75 (95% CI 0.63-0.91) for noncardiovascular death, both with CIs excluding 1, supporting the claim, though the paper appropriately labels it exploratory.
Evidence: Death from any cause: 566 (8.6%) vs 669 (10.2%), HR 0.84, 95% CI 0.75-0.94; noncardiovascular death: 199 (3.0%) vs 261 (4.0%), HR 0.75, 95% CI 0.63-0.91.
Death from any cause occurred in 566 patients (8.6%) in the tirzepatide group and 669 (10.2%) in the dulaglutide group (hazard ratio, 0.84; 95% CI, 0.75 to 0.94).
Resultsreviewer’s wording
supportedReviewer 1
The results were consistent among subgroups.
The paper states 'The results appeared to be consistent among subgroups stratified according to cardiovascular and diabetes-related clinical characteristics' and references Figure S9 for subgroup analysis, but the figure is not provided in the text. The claim is supported by the statement, but the actual data is in supplementary material.
Evidence: Subgroup analysis of the primary end point is shown in Figure S9.
“The results appeared to be consistent among subgroups stratified according to cardiovascular and diabetes-related clinical characteristics.”
Discussion ¶1Find in source
supportedReviewer 2
More gastrointestinal adverse events were observed in the tirzepatide group.
Table 3 shows higher rates of gastrointestinal events (42.5% vs 35.9%), nausea (25.1% vs 22.4%), and diarrhea (24.8% vs 19.1%) in the tirzepatide group.
Evidence: Table 3: Gastrointestinal adverse event 2827 (42.5%) vs 2387 (35.9%).
although more gastrointestinal adverse events were observed in the tirzepatide group.
Abstractreviewer’s wording
supportedReviewer 2
A prespecified secondary analysis suggested a possible lower incidence of death from any cause and of death from noncardiovascular causes in the tirzepatide group.
The results show death from any cause HR 0.84 (95% CI 0.75-0.94) and noncardiovascular death HR 0.75 (95% CI 0.63-0.91), supporting the claim, though the paper appropriately labels it exploratory.
Evidence: Death from any cause: 566 (8.6%) vs 669 (10.2%), HR 0.84 (95% CI 0.75-0.94); noncardiovascular death: 199 (3.0%) vs 261 (4.0%), HR 0.75 (95% CI 0.63-0.91).
a prespecified secondary analysis suggested a possible lower incidence of death from any cause and of death from noncardiovascular causes in the tirzepatide group than in the dulaglutide group.
Resultsreviewer’s wording

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

ADEQUATESurrogate endpoint
The primary endpoint is a composite of hard clinical outcomes: death from cardiovascular causes, myocardial infarction, or stroke. This is not a surrogate.
“The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke”
Find in source
ADEQUATEEffect size
The primary outcome shows noninferiority with a hazard ratio of 0.92 (95.3% CI, 0.83 to 1.01), with the upper bound below the prespecified noninferiority margin of 1.05. The effect is anchored to a clinically meaningful outcome and the noninferiority margin was chosen to preserve at least 50% of dulaglutide's efficacy.
“hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority”
Find in source

Data authenticity concerns

None found

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

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

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

Data/code availability incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites multiple prior trials showing GLP-1 receptor agonists reduce cardiovascular events and that tirzepatide improves metabolic risk factors, but notes the lack of a dedicated cardiovascular outcomes trial. The rationale for using dulaglutide as an active comparator is explicitly stated, and the noninferiority margin is justified. Limitations of prior work (small, short-duration pooled analyses) are acknowledged in the Discussion.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise by citing prior trials of GLP-1 receptor agonists and tirzepatide, and provides a logical rationale for the noninferiority design.

Evidence

“Clinical trials have shown that glucagon-like peptide-1 (GLP-1) receptor agonists reduce the incidence of major adverse cardiovascular events among patients with high cardiovascular risk and type 2 diabetes, 2-7 chronic kidney disease, 8,9 or obesity. 10”

Introduction ¶1Find in source

“The established role of GLP-1 receptor agonists in the management of type 2 diabetes in patients with high cardiovascular risk 2-7 precluded direct comparison of tirzepatide with a placebo control in a large, long-term clinical trial.”

Introduction ¶2Find in source

“Although a pooled analysis of previous trials of tirzepatide has examined the effect of tirzepatide on cardiovascular events, 28 those trials were small and short in duration.”

Discussion ¶2Find in source

PASSReviewer 2· 95% conf

The paper establishes a clear scientific premise by citing prior trials of GLP-1 receptor agonists and tirzepatide, and logically justifies the need for a cardiovascular outcomes trial.

Evidence

Introduction ¶1Find in source

paraphrase[Introduction, paragraph 1]

“However, data from a randomized, clinical trial of the effect of tirzepatide on cardiovascular outcomes have been lacking.”

“Although a pooled analysis of previous trials of tirzepatide has examined the effect of tirzepatide on cardiovascular events, 28 those trials were small and short in duration.”

Discussion ¶1Find in source

Randomization method (1:1 ratio, stratified by country and SGLT2 inhibitor use) is described, though the specific randomization algorithm is not detailed. Blinding is described (double-blind, sham dose-escalation). Power analysis is reported (1615 events for 90% power). Inclusion/exclusion criteria are detailed. Outlier handling is addressed via the modified intention-to-treat population and multiple imputation for missing data. Controls are inherent in the active comparator design. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial design is rigorous: double-blind, randomized, active-controlled, with a prespecified noninferiority margin, power calculation, and clear inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization and Trial Regimen]

“Eligible patients were randomly assigned in a 1:1 ratio to receive weekly subcutaneous injections of tirzepatide at a dose adjusted up to 15 mg or dulaglutide at a dose of 1.5 mg. Randomization was stratified according to country and the use of sodium–glucose cotransporter 2 (SGLT2) inhibitors at baseline.”

paraphrase[Methods, Randomization and Trial Regimen]

“Because the dose of dulaglutide remained at 1.5 mg throughout the trial, a sham dose-escalation scheme was used to maintain trial blinding.”

paraphrase[Methods, Statistical Analysis]

“We calculated that a minimum of 1615 primary end-point events would provide the trial with 90% power to determine the noninferiority of tirzepatide to dulaglutide (with a 10.5% lower risk of a primary end-point event with tirzepatide) and the superiority of tirzepatide to dulaglutide (with a 15% lower risk of a primary end-point event with tirzepatide) at a two-sided alpha level of 0.05.”

PASSReviewer 2· 95% conf

The trial design is rigorous: randomized, double-blind, active-comparator-controlled, with a prespecified noninferiority margin, power calculation, and clear inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization and Trial Regimen]

“Because the dose of dulaglutide remained at 1.5 mg throughout the trial, a sham dose-escalation scheme was used to maintain trial blinding.”

paraphrase[Methods, Statistical Analysis]

Sex is reported (29.0% women overall; Table 1 shows 28.7% and 29.3% in each group). Age, BMI, glycated hemoglobin, duration of diabetes, and comorbidities are reported. Demographics include race and ethnicity. Since both sexes are enrolled, sex_justified is not applicable. Species/strain and housing conditions are not applicable for a human trial.

Sub-criteria

demographicsADEQUATE

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· 95% conf

Demographic and clinical characteristics are comprehensively reported, including sex, age, race, and comorbidities.

Evidence

“29.0% were women”

AbstractFind in source

paraphrase[Results, Randomization, Patient Characteristics, and Follow-up]

“The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean BMI was 32.6±5.5, 65.0% of the patients had coronary artery disease, 19.2% had a history of stroke, 25.3% had peripheral artery disease, 20.3% had a history of heart failure, and the mean duration of diabetes was 14.7±8.8 years.”

“White race — no./total no. (%)† 5299/6501 (81.5) 5282/6492 (81.4)”

Table 1Find in source

PASSReviewer 2· 95% conf

Demographic and clinical characteristics are thoroughly reported, including age, sex, race, and key cardiovascular risk factors.

Evidence

“The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women”

AbstractFind in source

“White race — no./total no. (%)† 5299/6501 (81.5) 5282/6492 (81.4)”

Table 1Find in source

The protocol was approved by the ethics committee at each participating site, and all patients provided written informed consent. The trial is registered (NCT04255433). Regulatory compliance is implied by the trial being conducted under standard clinical trial regulations, though not explicitly named.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethics approval and informed consent are reported, and the trial is registered.

Evidence

paraphrase[Methods, Trial Organization and Oversight]

“The protocol was approved by the ethics committee at each participating site.”

paraphrase[Methods, Trial Population]

“All the patients provided written informed consent.”

“SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.”

ConclusionFind in source

PASSReviewer 2· 90% conf

Ethics approval and informed consent are adequately reported.

Evidence

paraphrase[Methods, Trial Organization and Oversight]

“The protocol was approved by the ethics committee at each participating site.”

paraphrase[Methods, Trial Population]

“All the patients provided written informed consent.”

“SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.”

ConclusionFind in source

Tirzepatide and dulaglutide are named with dosing regimens. The manufacturer (Eli Lilly) is implied as sponsor. Statistical software (SAS 9.4, RStudio 4.4.2) is identified. No antibodies, cell lines, or mycoplasma testing are applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational products (tirzepatide and dulaglutide) are identified with doses and regimen, and statistical software is identified.

Evidence

“Eligible patients were randomly assigned in a 1:1 ratio to receive weekly subcutaneous injections of tirzepatide at a dose adjusted up to 15 mg or dulaglutide at a dose of 1.5 mg.”

MethodsFind in source

“The statistical analyses were performed with SAS software, version 9.4 or higher (SAS Institute), and RStudio software, version 4.4.2 (Posit).”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

The investigational products (tirzepatide and dulaglutide) are identified with doses and regimen; statistical software is identified.

Evidence

“Eligible patients were randomly assigned in a 1:1 ratio to receive weekly subcutaneous injections of tirzepatide at a dose adjusted up to 15 mg or dulaglutide at a dose of 1.5 mg.”

MethodsFind in source

“The statistical analyses were performed with SAS software, version 9.4 or higher (SAS Institute), and RStudio software, version 4.4.2 (Posit).”

Statistical analysisFind in source

Tests are named (Cox proportional-hazards, ANCOVA, Fine-Gray). Assumptions are verified (proportionality assessed). Exact p-values are reported for the primary endpoint. Effect sizes with CIs are reported throughout. Software is identified. Data presentation follows clinical trial conventions (Kaplan-Meier curves, forest plots, per-group n). Mathematical plausibility is not applicable for large-N continuous outcomes.

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· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals for effect sizes.

Evidence

paraphrase[Methods, Statistical Analysis]

“The primary efficacy end point and the secondary end points that were assessed in time-to-clinical-event analyses were analyzed with Cox proportional-hazards models with treatment as the factor of interest and stratification according to SGLT2 inhibitor use at baseline.”

“P = 0.003 for noninferiority; P = 0.09 for superiority”

ResultsFind in source

paraphrase[Results, Efficacy End Points]

“hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01”

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with exact p-values for the primary endpoint and effect sizes with confidence intervals.

Evidence

“P = 0.003 for noninferiority; P = 0.09 for superiority”

AbstractFind in source

paraphrase[Abstract, Results]

“hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01”

paraphrase[Methods, Statistical Analysis]

“Proportionality of hazards assumptions was assessed within each stratum on the basis of SGLT2 inhibitor use at baseline, Schoenfeld residual plots, and a Kolmogorov-type supremum test.”

The paper states 'A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.' This is vague and does not specify the access mechanism. No repository deposit or accession numbers are mentioned. Code sharing is not applicable as no bespoke code is described.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the provided text; no repository or accession numbers are given.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of article, before Author Informati…Find in source

WARNReviewer 2· 80% conf

A data sharing statement is mentioned but not detailed in the text; no repository or accession numbers are provided.

Evidence

“A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.”

End of article, before Author Informati…Find in source

The trial is registered (NCT04255433). Methods are comprehensive. Limitations are explicitly discussed (no placebo, lack of diversity, SGLT2 imbalance). Conclusions are appropriately cautious, noting the exploratory nature of secondary findings. Funding and COI disclosures are provided.

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· 90% conf

The trial is registered, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.”

ConclusionFind in source

paraphrase[Discussion, paragraph 5]

“Our trial has limitations. The trial did not include a placebo group because the role of GLP-1 receptor agonists in the treatment of patients with diabetes and cardiovascular risk had been established.”

“Supported by Eli Lilly. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

End of articleFind in source

PASSReviewer 2· 95% conf

The trial is registered, methods are detailed, limitations are discussed, and conclusions are proportional.

Evidence

“SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.”

ConclusionFind in source

paraphrase[Discussion, paragraph 4]

“Supported by Eli Lilly. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

End of articleFind in source

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

ClinicalTrials.gov

NCT04255433

Broken references and links

None found · partly checked

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.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 31 references by DOI: 1 verified — 30 no DOI (shown, not verified).

NO DOI
The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Semaglutide and cardiovascular outcomes in patients with type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Liraglutide and cardiovascular outcomes in type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cardiovascular and kidney outcomes and mortality with long-acting injectable and oral glucagon-like peptide 1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of randomized trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Semaglutide and cardiovascular outcomes in obesity without diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pharmacologic approaches to glycemic treatment: standards of care in diabetes — 2023
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide as compared with semaglutide for the treatment of obesity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
New creatinine- and cystatin C–based equations to estimate GFR without race
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genetically predicted glucose-dependent insulinotropic polypeptide (GIP) levels and cardiovascular disease risk are driven by distinct causal variants in the GIPR region
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality: a prospective study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

2 minor

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

No major wording or formatting errors. 2 minor suggestions below.

2 copyedit issues flagged: mostly typo, consistency.

MINORtypoResults, Randomization, Patient Characteristics, and Follow-up
“eligibile”
→ eligible
Typographical error in the word 'eligible'.
MINORconsistencyTable 2, footnote
“The confidence level for the primary end point was adjusted for the interim efficacy analysis; shown is the 95.3% confidence interval, which corresponds to the nominal two-sided significance level of 0.047.”
→ Ensure consistency in reporting the confidence level as 95.3% throughout the text and tables.
The abstract and results consistently use 95.3% CI, but the footnote explains the adjustment; no major inconsistency.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published paper is robust and well-reported. An informed reader should note the vague data sharing statement as a limitation for reproducibility; the authors should consider issuing a correction or supplement with a concrete data access plan. No other issues warrant an erratum or re-analysis.

1.
HIGHdata code
Replace the vague data sharing statement with a concrete description of the data access mechanism, including the repository name (e.g., Vivli, YODA) or data access committee, conditions, and timeline.
The current statement is insufficient for reproducibility and does not meet journal standards for data availability.
2.
HIGHreporting
Add an explicit statement about adherence to the CONSORT reporting guideline in the Methods or a separate section, and mention that the checklist is available as supplementary material.
Explicit reporting guideline adherence is expected for clinical trials and is currently missing.
3.
MEDIUMdata code
Consider providing a link to the full protocol and statistical analysis plan in the data availability statement, as they are currently only mentioned as available with the full text.
Access to the full protocol and SAP enhances transparency and reproducibility.
4.
MEDIUMdata code
If any bespoke analysis code was used beyond standard SAS/R functions, share it in a public repository (e.g., GitHub) with a DOI.
Code sharing further supports reproducibility, even if the code is standard.
5.
LOWcopyedit
Correct the typo 'eligibile' to 'eligible' in the Results section.
Minor typographical error that should be corrected for clarity.
6.
LOWreporting
Clarify the data sharing statement in the main text to include the URL or platform where the data sharing statement can be accessed, to avoid ambiguity.
The current reference to 'at NEJM.org' is vague; a direct link would be more helpful.

Full text (44,037 chars)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

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.

Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.

DOI

10.1056/NEJMoa2505928

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-20