GLP-1RA bests aspirin for CRC prevention

Use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) appears to confer greater protection against the development of colorectal cancer (CRC) as compared with aspirin, according to a retrospective study.

In a large propensity-matched cohort, GLP-1RA users had a 36-percent lower risk of CRC than aspirin users (hazard ratio [HR], 0.643, 95 percent confidence interval [CI], 0.531–0.778), reported first author Dr Colton Jones from the University of Texas San Antonio in San Antonio, Texas, US. [ASCO GI 2026, abstract 18]

The CRC risk reduction with GLP-1RA was even greater for individuals who were at high risk (HR, 0.579, 95 percent CI, 0.401–0.837), which Jones defined as those who had first-degree relatives with CRC, those with known genetic predisposition to CRC, and those with known high-risk comorbidities such as ulcerative colitis and Crohn’s disease.

Among GLP-1RA users, the CRC risk reduction was more pronounced in subgroup of individuals ages 18–44 years (HR, 0.583, 95 percent CI, 0.349–0.974) and was consistently observed regardless of BMI (<29 kg/m²: HR, 0.438, 95 percent CI, 0.298–0.643; >30 kg/m²: HR, 0.611, 95 percent CI, 0.492–0.759) and diabetes status (diabetics: HR, 0.746, 95 percent CI, 0.511–0.982; nondiabetics: HR, 0.588, 95 percent CI, 0.471–0.734).

Finally, the beneficial effect of GLP-1RA on CRC risk was especially evident for liraglutide (HR, 0.436, 95 percent CI, 0.220–0.861), dulaglutide (HR, 0,471, 95 percent CI, 0.358–0.618), and semaglutide (HR, 0.631, 95 percent CI, 0.492–0.810).

In terms of safety, GLP1-RA users had a higher incidence of diarrhoea (6.8 percent vs 5.4 percent; HR, 1.131, 95 percent CI, 1.096–1.166; p=0.0001) and abdominal pain (19 percent vs 16.3 percent; HR, 1.055, 95 percent CI, 1.036–1.075; p=0.0001) than aspirin users. Jones noted that these events are known side effects of both medications.

On the other hand, aspirin users were more likely to have gastrointestinal bleeding (2 percent vs 2.1 percent; HR, 0.852, 95 percent CI, 0.809–0.898; p=0.018), gastric ulcers (0.5 percent vs 0.55 percent; HR, 0.815, 95 percent CI, 0.735–0.904; p=0.038), and acute kidney injury (1.15 percent vs 2.8 percent; HR, 0.369, 95 percent CI, 0.348–0.391; p=0.0001).

“The large population size of this study and the favourable safety profile of GLP-1RAs vs aspirin could underscore a potential public health impact,” given that GLP-1RAs are widely used in the treatment of diabetes and obesity, Jones said.

GLP-1RAs may confer anticancer benefits by exerting anti-inflammatory and antiproliferative effects in CRC cell lines through inhibition of the PI3K/Akt/mTOR pathway, Jones explained.

The next step in the research is to confirm the present findings in randomized clinical trials, he added.

For the study, Jones and colleagues used de-identified data from the TriNetX database and established a propensity-matched cohort of 140,828 GLP-1RA users and 140,828 aspirin users. The average age at index event was 58 years, with females and Whites making up 67 percent of the cohort.

The median follow-up duration was 6 years for GLP-1RA users and 5 years for aspirin users.