GLP-1 Associated With Colorectal Cancer Prevention, Research Finds

GLP-1 receptor agonists (GLP-1Ras) significantly outperformed Aspirin (acetylsalicylic acid) in reducing the risk of colorectal cancer, regardless of a patient’s weight or diabetes status, according to research presented at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

At a median six-year follow-up for GLP-1RA users and five years for aspirin users, the use of a GLP-1RA reduced the risk of CRC by 35.7% compared with aspirin use. In high-risk patients, the risk was reduced by 42.1%. High risk was defined as having a first-degree relative with CRC, those with known genetic predisposition, and those with known high-risk comorbidities including ulcerative colitis and Crohn’s disease.

In a presentation of the data, Dr. Colton Frisco Jones, a hematology oncology fellow at The University of Texas, San Antonio Mays Cancer Center, described the study as “the first real-world head-to-head comparison of the efficacy and safety of GLP1-RA versus Aspirin for the primary prevention of CRC.”

“The large population size of this study and the favorable safety profile of GLP-1s versus Aspirin could underscore a potential public health impact,” said Jones. “These findings warrant prospective validation.”

Younger patients (ages 18 to 44) saw a greater reduction in the risk of CRC at 41.7% compared with a 21% risk reduction in those ages 45 to 64 and a 27.1% risk reduction in those age 65 or older.

Benefit was seen regardless of diabetes or BMI statuses. Patients with diabetes had a 25.4% CRC risk reduction and those without diabetes had a 41.2% risk reduction when taking a GLP-1RA.

Between GLP-1RAs, the following incidence reductions relative to Aspirin use were observed:

• Semaglutide, 36.9%
• Tirzepatide, 28.9%
• Liraglutide, 56.4%
• Dulaglutide, 52.9%

Those with a BMI over 30 had a 38.9% CRC risk reduction with GLP-1RA use versus 56.2% in those with a BMI less than 29.

Safety Events in Patients Taking a GLP-1RA versus Aspirin

Patients taking Aspirin had a higher rate of gastrointestinal bleeding (2.1%) versus those taking a GLP-1RA. The same was true for gastric ulcers (0.55% versus 0.5%) and acute kidney injury (2.8% versus 1.15%).

Those taking a GLP-1RA had higher incidence of nausea and vomiting (10.5% versus 9.7%), diarrhea (6.8% versus 5.4%) and abdominal pain (19% versus 16.3%).

Patient Selection and Observation

The primary end point for this study was CRC incidence with a secondary end point of incidence of adverse events related to GLP1-RA and Aspirin use.

Patients 18 to 90 years old from Jan. 1, 2000 to Jan. 1, 2024, were included, with the exclusion of patients taking other non-steroidal aromatase inhibitors (NSAIDs) besides Aspirin as well as those taking any hypoglycemic medications aside from GLP1-RA. Additionally, those with CRC prior to the study window were excluded. After exclusions, 140,828 patients in each arm were matched to either cohort A, GLP-1RA users, or cohort B, aspirin users.

The average age at index event was 58 ±13.5 in cohort A and 58 ±13.7 in cohort B\. Most patients were White (67% in each cohort) and female (67% in each cohort).

Colton and co-authors used data from the TrinetX database, containing information on 150 million patients from 106 health organizations. Patients from cohort A were matched to patients in cohort B via propensity score matching. Clinically meaningful sensitivity and subgroup analyses were performed, and those with outcomes before the study window were excluded.

GLP-1RAs in CRC Risk Reduction

Colton noted that Aspirin has been investigated as a means of CRC prevention but due to its “modest efficacy” and increased risk of bleeding, its use is limited; further, GLP-1RAs have been shown to have anti-inflammatory and antineoplastic due to PI3K/AKT/mTOR pathway inhibition. For these reasons, Colton and co-authors set to explore the use of GLP-1RAs as primary prevention for CRC.

Reference

“Glucagon-like peptide-1 receptor agonist vs aspirin for primary prevention of colorectal cancer: evidence from a real-world head-to-head comparison,” by Dr. Colton Frisco Jones et al., J Clin Oncol.

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