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Related Experiment Videos

Exploratory Cardiovascular Risk Modeling of Orforglipron Using the PREVENT Equations Compared with the Pooled Cohort

Adir Alper1, Adina Fagin2, Aditya Karthikeyan2

  • 1Jacobi Medical Center, 1400 Pelham Parkway, Bronx, New York, NY, 10461, USA. alpera@nychhc.org.

High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension
|July 15, 2026
PubMed
Summary

The AHA PREVENT equations provide a more comprehensive assessment of orforglipron

Keywords:
ASCVDCKM syndromeCardiovascular riskGLP-1 receptor agonistHbA1cOrforglipronPREVENTPooled cohort equations

Related Experiment Videos

Area of Science:

  • Cardiovascular medicine
  • Pharmacology
  • Metabolic disease research

Background:

  • Orforglipron, an oral GLP-1 receptor agonist, shows promise for improving cardiometabolic risk factors.
  • Traditional risk calculators like the 2013 Pooled Cohort Equations (PCE) do not incorporate key variables such as BMI, eGFR, and HbA1c.
  • The 2023 AHA PREVENT equations offer a more nuanced approach to cardiovascular risk assessment.

Purpose of the Study:

  • To compare cardiovascular risk reduction estimates for orforglipron using the 2013 PCE versus the 2023 AHA PREVENT equations.
  • To quantify the additional cardiometabolic benefits captured by the PREVENT equations.

Main Methods:

  • Post-hoc analysis using pooled data from five orforglipron RCTs.
  • Application of 2013 PCE and 2023 PREVENT equations (base and HbA1c-enhanced) to hypothetical patient profiles.
  • Calculation of 10- and 30-year CVD risk at baseline and post-treatment across various orforglipron doses.

Main Results:

  • The PREVENT HbA1c-enhanced model projected 75-90% greater risk reductions than PCE.
  • For a representative patient, PREVENT projected a 31.4% 10-year RRR (vs. 16.8% by PCE), driven by BMI and HbA1c.
  • PREVENT also estimated a 22.4% reduction in 10-year heart failure risk, a metric absent in PCE.

Conclusions:

  • The AHA PREVENT equations may more accurately capture orforglipron's cardiovascular benefits compared to PCE.
  • Exclusive reliance on PCE may underestimate orforglipron's cardiometabolic impact.
  • PREVENT offers a more comprehensive framework for assessing therapies targeting the cardiovascular-kidney-metabolic axis, pending validation in outcome trials.