C Jones. J Clin Oncol 44, 2026: suppl 2; abstract 18 (presented at ASCO 2026). Open Access! GLP-1 receptor agonist vs aspirin for primary prevention of colorectal cancer: Evidence from a real-world head-to-head comparison

Methods: Using de-identified data from TriNetX, which encompasses 150 million patients across 106 health organizations. GLP-1RA users were matched to aspirin users utilizing propensity score matching. The index date was defined as the first documented prescription or administration of either therapy, with follow-up beginning 6 months post-index event. Median follow-up was 2,153 days for GLP-1RA users and 1,743 days for aspirin users. 281,656 patients were analyzed (140,828 per cohort).

Key findings:

• Colorectal cancer (CRC) incidence was 0.13% (183/140,758) in GLP-1RA users vs 0.176% (247/140,692) in aspirin users
• GLP-1RA use was associated with a 26% lower risk of CRC [RR: 0.741 (0.612–0.896)].This benefit was consistent across sensitivity analyses at 12 months [RR: 0.738 (0.605–0.900)] and 36 months [RR: 0.779 (0.620–0.979)]
• Four different GLP-1s were analyzed: HR of 0.436 for liraglutide, 0.471 with dulaglutide, 0.631 with semaglutide, and 0.711 with tirzepatide

The exact mechanism where GLP-1s may exert a protective effect is unclear; perhaps, it is related to a reduction in adverse metabolic parameters and inflammation.

My take: Potential chemopreventive effects are unlikely to be a reason to use GLP-1s in the near future, but may be an added benefit.

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