Dr Jones on the Rationale for Comparing CRC Risk Reduction With GLP-1 Agonists vs Aspirin

“GLP-1s had, overall, better efficacy compared [with] aspirin and better tolerability... This is the first study to compare a new drug, GLP-1s, to what was previously the standard of care, aspirin, in a head-to-head fashion."

Colton Jones, MD, a hematology and oncology fellow at The University of Texas San Antonio, explained the rationale for a landmark comparison between glucagon-like peptide-1 (GLP-1) receptor agonists and aspirin for the primary prevention of colorectal cancer (CRC).

For years, aspirin served as the pharmacologic standard for CRC prevention, Jones began. However, clinical data from the observational ASPREE study (NCT01038583) shifted this paradigm, revealing that older patients who received aspirin had a higher likelihood of presenting with advanced or metastatic disease and that aspirin provided no significant reduction in CRC risk and increased the risk of major brain bleeding. These safety and efficacy concerns prompted the United States Preventive Services Task Force to remove its Category B recommendation for aspirin in CRC primary prevention, leaving the field without an established preventive standard.

To address this gap, Jones and colleagues conducted a retrospective, real-world comparison utilizing de-identified data from the TriNetX network, which represents approximately 150 million patients across 106 health care organizations. The study population included 281,656 participants between the ages of 18 and 90 who were enrolled between January 1, 2000, and January 1, 2024. Using propensity score matching for demographics and clinical characteristics, the analysis cohort was divided into 2 equal groups of 140,828 patients receiving either GLP-1 receptor agonists or aspirin. A 6-month lead-in period was incorporated post-index date.

Data shared at the 2026 Gastrointestinal Cancer Symposium showed that, at a median follow-up of 6 years, GLP-1 receptor agonist use was associated with a 35.7% lower risk of CRC overall vs aspirin (HR, 0.643; 95% CI, 0.531-0.778). Moreover, patients defined as high-risk based on their health or family history were 42.1% less likely to develop CRC than those in the aspirin cohort (HR, 0.579; 95% CI, 0.401-0.837). Jones noted that this was the first study to evaluate these strategies in a head-to-head fashion, evaluating both efficacy and tolerability. Ultimately, the data showed that GLP-1s offered superior efficacy and better tolerability, suggesting they may represent a viable new standard for pharmacologic prevention in CRC.

To learn more about this topic, be sure to check out our accompanying article featuring insights from Drs Jones and Saltzman.