Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. According to the American Cancer Society, in 2025, about 154,270 individuals were diagnosed with colorectal cancer, and approximately 53,000 individuals died from the disease.
Although some studies have suggested that regular, long-term use of low-dose aspirin may help prevent colorectal cancer, the drug can cause serious side effects (including bleeding) and is no longer recommended for the prevention of colorectal cancer. Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may also confer anticancer benefits by exerting anti-inflammatory and antiproliferative effects in colorectal cancer cell lines through inhibition of the PI3K/AKT/mTOR pathway.
A large head-to-head comparison of GLP-1 RAs and aspirin for primary colorectal cancer prevention has found that individuals who took GLP-1 RAs were 36% less likely to develop colorectal cancer compared with those who took aspirin. Individuals taking GLP-1 RAs whose health or family history put them at higher risk of developing colorectal cancer were nearly 42% less likely to develop the cancer than those who took aspirin. The study will be presented by Jones et al during the 2026 ASCO Gastrointestinal Cancers Symposium, taking place January 8–10 in San Francisco (Abstract 18).
Study Methodology
The researchers used de-identified data from 281,656 participants in TriNetX, a global network of health-care organizations. The GLP-1 RA users were matched to the aspirin users (140,828 per cohort) with similar demographics. The mean age of the participants was 58 years; 69% were female; 67% were White, 12% were Black, and 2.3% were Asian.
The primary endpoint of the study was colorectal cancer incidence. The index date was defined as the first documented prescription or administration of either therapy, with follow-up beginning 6 months post–index event. Sensitivity analysis was performed at 12 and 36 months. Median follow-up was about 5.9 years for GLP-1 RA users and 4.7 days for aspirin users. Subgroup analysis included age, body mass index, diabetes status, tobacco history, atherosclerotic disease, and GLP-1 RA type.
Results
The researchers found that individuals who took GLP-1 RAs were 36% less likely to be diagnosed with colorectal cancer compared with those who took aspirin. Of the participants whose health or family history put them at greater risk of developing colorectal cancer, those who took GLP-1 RAs were nearly 43% less likely to get the cancer than individuals who took aspirin.
Across both cohorts, the researchers found that acute kidney injury, stomach ulcers, and gastrointestinal bleeding were less common in the GLP-1 RA cohort than those in the aspirin cohort; diarrhea and abdominal pain were more common in the GLP-1 RA cohort than in the aspirin cohort; and nausea and vomiting were experienced by participants in both cohorts.
Additional results showed that:
- The benefit for any one person was small. According to the statistics, more than 2,000 individuals would need to be treated with a GLP-1 RA for one individual to have a lower risk of developing colorectal cancer. However, a recent KFF Health Tracking Poll found that 6% of adults were taking these medicines. That could mean as many as 20 million Americans are already using GLP-1 RA and that many of them could have a reduced risk of developing colorectal cancer.
- GLP-1 RAs reduced colorectal cancer risk in participants who began the medicine before age 45, and they also reduced risk regardless of whether participants had obesity or diabetes. However, they did not reduce the risk of colorectal cancer in individuals who used tobacco or who had atherosclerosis.
- In total, the GLP-1 RA agents studied showed a reduced risk of colorectal cancer. However, when studied individually, only the effect of semaglutide, liraglutide, and dulaglutide was significant; tirzepatide and exenatide did not show the same significance in this study.
The researchers concluded that the study results, “along with the favorable safety profile of GLP-1 RAs, could underscore a potential public health impact and warrant prospective validation in randomized clinical trials.”
GLP-1 RAs May Offer a Safe Option for Colorectal Cancer Prevention
“While aspirin has been studied for colorectal cancer prevention, its modest benefit and bleeding risks limit its use,” said lead study author Colton Jones, MD, a hematology and oncology fellow at The University of Texas San Antonio. “GLP-1 RAs, now widely prescribed for diabetes and obesity, may offer a safer option for both metabolic control and cancer prevention. This study is important because it provides the first large-scale, real-world evidence comparing aspirin and GLP-1 RAs directly.”
ASCO Perspective
“GLP-1 RAs may have benefits far beyond the waistline. These findings show that they may be an important part of cancer prevention treatment strategies as well. The preventive benefits of aspirin, nonsteroidal anti-inflammatory drugs, and statins in the development of colorectal cancer have been investigated for years. This real-world study suggests that the GLP-1 RAs may have an exciting role in this area. Further research is certainly a priority to understand the promise of these drugs to help prevent cancer,” said Joel Saltzman, MD, an ASCO Expert in gastrointestinal cancers and Vice Chair of Regional Oncology at Taussig Cancer Center, Cleveland Clinic.
Disclosure: This study did not receive outside funding. For full disclosures of the study authors, visit coi.asco.org.
