Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an Exenatide Study of Cardiovascular Event Lowering (EXSCEL) post hoc analysis
Authors' conclusion
These model simulations explain only a modest proportion of the impact of observed EQW-induced changes in conventional CV risk factors on EXSCEL outcomes, apart from hHF and MI. Up to 1-year changes in conventional risk factors did not mediate the observed ACM risk reduction.
Study context
- Population
- EXSCEL participants with T2D
- Comparison
- Once-weekly exenatide vs placebo
- Primary endpoint
- Proportion of observed relative risk reductions in CV outcomes (MACE, ACM, CV death, MI, stroke, hospitalization for heart failure (hHF)) explained by model-simulated EQW-induced changes in conventional CV risk factors
Methodological detailsmodelling study using validated T2D-specific clinical outcomes model, mediation analysis (Cox regression)
- Modelling study using validated T2D-specific clinical outcomes model
- Mediation analysis (Cox regression)
Primary result
As reported in the abstract
Proportion of observed relative risk reduction explained by model simulations
- Major adverse CV event (MACE)
- 29%
- All-cause mortality (ACM)
- 15%
- Cardiovascular (CV) death
- 18%
- Stroke
- 29%
- Hospitalization for HF
- 67%
- Myocardial infarction (MI)
- 200%
Further findings
Mediation of EQW effect on ACM · baseline to 6 or 12 months
- Changes in HbA1c, blood pressure, heart rate, LDL-C, TG and weight did not mediate the EQW effect on ACM
Original publication
Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis. Cardiovasc Diabetol. Published 23 August 2025. doi:10.
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