The use of GLP-1 receptor antagonist (GLP-1RA) therapy has led to a greater reduction in colorectal cancer (CRC) incidence than has been observed with aspirin, according to research presented at the ASCO Gastrointestinal Cancers Symposium 2026.
“The large population size of this study and the favorable safety profile of GLP-1s versus aspirin could underscore a potential public health impact, and these findings warrant prospective validation,” said study presenter Colton Jones, MD, of The University of Texas Health Science Center in San Antonio.
The study was based on deidentified data obtained from the TriNetX database, which includes records for approximately 150 million patients throughout 106 health systems. Patients included in the analysis were aged 18 to 90 years between January 1, 2000, and January 1, 2024.
The researchers used propensity score matching to match patients using GLP-1RA therapy to those using aspirin. Patients excluded from the analyses had CRC, were receiving NSAIDS besides aspirin and/or hypoglycemic medications besides GLP-1RAs, or were deceased.
Among eligible patients, 149,115 were receiving GLP-1RAs and 3,011,724 were receiving aspirin. With matching, the study included 140,828 patients in each cohort. After matching, average patient ages at index event were 58 ± 13.5 years in the GLP-1RA group and 58 ± 13.7 years in the aspirin group. In each group, 67% of patients were female, 67% were White, 12% were Black, and 2.3% were Asian.
Overall, the incidence of CRC among users of GLP-1RAs appeared to be approximately 36% lower than that observed among aspirin users (hazard ratio [HR]0.643; 95% CI, 0.531-0.778). The difference was greater in patients considered to be high risk (HR, 0.579; 95% CI, 0.401-0.837).
Lower CRC incidence was also observed in the GLP-1RA group for patients with or without diabetes. For those with diabetes, in the comparison of GLP-1RAs and aspirin, the HR for CRC incidence was 0.746 (95% CI, 0.511-0.982). For patients without diabetes, the HR was 0.588 (95% CI, 0.471-0.734). The researchers observed lower CRC incidence regardless of whether the patients used semaglutide, liraglutide, or dulaglutide.
Gastrointestinal bleeding occurred in 2% of GLP-1RA users and 2.1% of aspirin users (HR, 0.852; 95% CI, 0.809-0.898; P =.018). Gastric ulcers occurred in 0.5% and 0.55%, respectively (HR, 0.815; 95% CI, 0.735-0.904; P =.038), and acute kidney injury occurred in 1.15% and 2.8%, respectively (HR, 0.369; 95% CI, 0.348-0.391; P =.0001).
Diarrhea (HR, 1.131; 95% CI, 1.096-1.166; P =.0001) and abdominal pain (HR, 1.055; 95% CI, 1.036-1.075; P =.0001) were more common with GLP-1RA use than with aspirin use.
“So in conclusion, in this real-world, head-to-head comparison of GLP-1 use versus aspirin, GLP-1 users were associated with a 36% reduction in colorectal cancer incidence, and this reduction was even greater in patients who had high-risk features,” Dr Jones said in his presentation. Disclosures: There was no funding listed for this study. One study author disclosed conflicts of interest. Please see the original reference for complete disclosures.