Dr Jones on the Protective Benefit and Tolerability of GLP-1 Agonists vs Aspirin for CRC Prevention

"Overall, [GLP-1s had] better efficacy compared [with] aspirin and better tolerability, which is what we need for our patients."

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

To evaluate the potential of GLP-1s for CRC risk reduction, Jones and colleagues conducted a retrospective, real-world analysis utilizing de-identified data from the TriNetX network, which represents approximately 150 million patients across 106 health care organizations. The study population comprised 281,656 participants between the ages of 18 and 90 years enrolled between January 1, 2000, and January 1, 2024. Through propensity score matching for demographics and clinical characteristics, the cohort was divided into 2 equal groups of 140,828 patients receiving either GLP-1 receptor agonists or aspirin.

Results from this study were first reported at the 2026 Gastrointestinal Cancer Symposium and demonstrated 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 compared with aspirin (HR, 0.643; 95% CI, 0.531-0.778). The protective benefit was even more pronounced among high-risk patients—defined by family history, genetic predisposition, or specific comorbidities—who experienced a 42.1% lower risk of developing CRC compared with those in the aspirin cohort (HR, 0.579; 95% CI, 0.401-0.837).

Beyond efficacy, Jones emphasized that the GLP-1 group exhibited superior tolerability, with a lower risk of bleeding and gastrointestinal ulcers. Although GLP-1s were associated with an expected slight increase in nausea and vomiting, the overall profile was considered more favorable. Jones concluded that this first head-to-head evaluation suggests GLP-1 receptor agonists may represent a new standard for pharmacologic CRC prevention.

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