GLP-1 Receptor Agonists Linked to Lower Colorectal Cancer Risk Than Aspirin in Real-World Analysis
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with a significantly lower incidence of colorectal cancer (CRC) compared with aspirin in a large, real-world head-to-head analysis, suggesting a potential role for GLP-1RAs in primary CRC prevention.
Using deidentified data from the TriNetX research network, investigators analyzed records from 150 million patients across 106 health care organizations. After propensity score matching for demographic and clinical confounders, 281,656 patients were included, evenly divided between GLP-1RA users and aspirin users. Median follow-up exceeded 5 years in the GLP-1RA cohort and nearly 4.8 years in the aspirin cohort.
CRC incidence was lower among GLP-1RA users, occurring in 0.13% of patients compared with 0.176% in the aspirin group. This translated to a 26% relative reduction in CRC risk for GLP-1RA therapy (risk ratio, 0.741). The authors reported that “GLP-1RA use was associated with a 26% lower risk of CRC,” with consistent findings across sensitivity analyses at 12 and 36 months.
Risk reduction was observed across multiple subgroups, including patients with and without obesity and those with or without diabetes. Notably, the strongest associations were seen in patients with elevated A1c levels, in whom GLP-1RA use was associated with a 60% relative risk reduction. Among individual agents, semaglutide was the only GLP-1RA associated with a statistically significant reduction in CRC risk. No significant associations were observed among tobacco users or patients with established atherosclerotic disease.
The absolute risk reduction was modest, with a number needed to treat of 2198, reflecting the low baseline incidence of CRC in a general population cohort. Still, the authors concluded that this analysis represents “the first large-scale, real-world, head-to-head comparison of GLP-1RA versus aspirin for primary CRC prevention.”
For gastroenterologists, the key takeaway is that GLP-1RAs may confer CRC risk reduction beyond metabolic benefits and appear more effective than aspirin in this setting. The authors emphasized that these findings warrant confirmation in prospective randomized clinical trials before influencing prevention guidelines.
Reference
Jones C. GLP-1 receptor agonist vs aspirin for primary prevention of colorectal cancer: Evidence from a real-world head-to-head comparison. Presented at: American Society of Clinical Oncology. May 30-June 5, 2025. Chicago, Illinois.
