Exploratory Cardiovascular Risk Modeling of Orforglipron Using the PREVENT Equations Compared with the Pooled Cohort Equations: A Post-Hoc Analysis from a Systematic Review and Meta-analysis.

Alper A, Fagin A, Karthikeyan A, Karp A, Terashima R, Murli H, Gershon A, Faillace R

High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension15 Jul 2026

PMID42458197DOI10.1007/s40292-026-00814-4PepBankPUB-42458197

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study7

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone7

In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Orforglipron.

01Computer modelNot a test of Orforglipron aloneIn silicoOther
In hypothetical profiles, PREVENT projected orforglipron-related relative cardiovascular risk reductions approximately 75-90% larger than PCE projections.
In plain wordsIn computer models, PREVENT projected larger cardiovascular risk reductions with orforglipron than PCE.
Peptide
Orforglipron
Outcome
IncreaseRelative cardiovascular risk reduction across models
Study
n: not reported in source
Hypothetical patient profiles
Comparator
PCE
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
In these modeled scenarios, the PREVENT HbA1c-enhanced model projected model-dependent relative risk reductions approximately 75-90% larger than those generated by the PCE across all patient profiles and dose tiers.
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819701
02Computer modelNot a test of Orforglipron aloneIn silicoOther
In a hypothetical man with diabetes, PCE projected a 16.8% cardiovascular risk reduction with modeled orforglipron treatment.
In plain wordsIn a hypothetical man with diabetes, PCE projected lower cardiovascular risk after modeled orforglipron treatment.
Peptide
Orforglipron
Outcome
DecreaseProjected cardiovascular risk reduction with PCE
Study
n: not reported in source
Hypothetical patient profiles
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Measurements
10-year relative risk reduction
16.8%
PCE, 36 mg
Source sentences
Summary
the PCE estimated a 10-year RRR of 16.8% at the 36 mg dose, whereas PREVENT HbA1c-enhanced projected an RRR of 31.4% at the same dose
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819702
03Computer modelNot a test of Orforglipron aloneIn silicoOther
In a hypothetical man with diabetes, PREVENT projected a 31.4% cardiovascular risk reduction with modeled orforglipron treatment.
In plain wordsIn a hypothetical man with diabetes, PREVENT projected lower cardiovascular risk after modeled orforglipron treatment.
Peptide
Orforglipron
Outcome
DecreaseProjected cardiovascular risk reduction with PREVENT
Study
n: not reported in source
Hypothetical patient profiles
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Measurements
10-year relative risk reduction
31.4%
PREVENT, 36 mg
Source sentences
Summary
the PCE estimated a 10-year RRR of 16.8% at the 36 mg dose, whereas PREVENT HbA1c-enhanced projected an RRR of 31.4% at the same dose
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819703
04Computer modelNot a test of Orforglipron aloneIn silicoOther
In hypothetical profiles, HbA1c accounted for approximately one-third of PREVENT's projected total risk reduction with orforglipron.
In plain wordsIn computer models, HbA1c accounted for approximately one-third of the projected risk reduction with orforglipron.
Peptide
Orforglipron
Outcome
Not applicableHbA1c contribution to projected risk reduction
Study
n: not reported in source
Hypothetical patient profiles
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Approximately one-third of the projected total risk reduction by PREVENT was attributable to HbA1c alone, a dimension the PCE structurally cannot assess.
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819704
05Computer modelNot a test of Orforglipron aloneIn silicoOther
In hypothetical profiles, PREVENT projected a 22.4% reduction in heart failure risk with modeled orforglipron treatment.
In plain wordsIn computer models, PREVENT projected lower heart failure risk after modeled orforglipron treatment.
Peptide
Orforglipron
Outcome
DecreaseProjected heart failure risk
Study
n: not reported in source
Hypothetical patient profiles
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Measurements
10-year heart failure risk reduction
22.4%
PREVENT
Source sentences
Summary
PREVENT also projected a 22.4% reduction in 10-year heart failure risk, a dimension absent from the PCE.
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819705
06Computer modelNot a test of Orforglipron aloneIn silicoOther
In hypothetical profiles used to model orforglipron, PREVENT yielded lower baseline cardiovascular risk estimates than PCE.
In plain wordsIn computer models for orforglipron, PREVENT estimated lower baseline cardiovascular risk than PCE.
Peptide
Orforglipron
Outcome
DecreaseBaseline risk estimates
Study
n: not reported in source
Hypothetical patient profiles
Comparator
PCE
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
PREVENT yielded lower baseline risk estimates than the PCE, consistent with known PCE overestimation.
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819706
07Computer modelNot a test of Orforglipron aloneIn silicoOther
In modeled Profile A, PREVENT projected a lower ASCVD risk category at all orforglipron doses, whereas PCE projected no reclassification.
In plain wordsIn computer models, PREVENT projected a lower risk category with orforglipron, whereas PCE projected no category change.
Peptide
Orforglipron
Outcome
DecreaseASCVD risk category reclassification
Study
n: not reported in source
Hypothetical patient profiles
Comparator
PCE
Analysis
Exploratory
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
Notably, the PREVENT ASCVD-specific model projected reclassification of Profile A from borderline to low risk (< 5.0%) at all doses, whereas the PCE showed no reclassification from intermediate risk at any dose.
2 context sentences(design, population, supporting numbers)
Summary · context
In this post-hoc analysis, we applied pooled effect estimates from our systematic review and meta-analysis of five orforglipron RCTs to representative hypothetical patient profiles.
Summary · context
Absolute and relative risk reductions were compared across tools.
In this study, Orforglipron was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Orforglipron.
Report a problemFND-4245819707

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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Exploratory Cardiovascular Risk Modeling of Orforglipron Using the PREVENT Equations Compared with the Pooled Cohort Equations: A Post-Hoc Analysis from a Systematic Review and Meta-analysis.

Summary

Results from this study7

Studies that did not test the peptide alone7

Version history

Subjects

Publication types

MeSH terms

Keywords