GLP-1 Receptor Agonists Linked to Lower Risk of CRC Among Patients With IBD
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were associated with a significantly lower 5-year incidence of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD), according to a large retrospective analysis of US healthcare data from the TriNetX database.
Presented at the 2026 ASCO Breakthrough Meeting in Singapore, these findings suggest a potential protective association in a population already known to have an elevated risk of CRC, although prospective studies are needed to confirm the results.
Study Findings
Researchers conducted a retrospective cohort study using the TriNetX database, which includes healthcare records from more than 150 million patients across the United States. The analysis evaluated whether GLP-1 RA use was associated with CRC incidence among adults with pre-existing IBD and in a subgroup of patients with both IBD and type 2 diabetes mellitus (T2DM).
The GLP-1 RA cohort included patients treated with semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, or lixisenatide. Investigators used propensity score matching to balance demographic and clinical characteristics, including age, sex, race, tobacco and alcohol use, obesity, hypertension, hyperlipidemia, IBD subtype, corticosteroid use, immunosuppressive and biologic therapy, and other diabetes medications.
Among 1,137,300 patients with IBD, 70,303 had received a GLP-1 RA; after matching, 69,221 patients were included in the primary analysis. Over 5 years, GLP-1 RA users had a significantly lower incidence of CRC than nonusers (0.20% vs 0.43%), corresponding to an odds ratio (OR) of 0.49 (95% CI, 0.30-0.57; P<0.001).
The investigators also analyzed 209,649 patients with both IBD and T2DM, including 38,567 GLP-1 RA users. Following propensity score matching, 37,740 patients remained in the analysis. In this subgroup, GLP-1 RA therapy was likewise associated with a reduced 5-year CRC incidence compared with nonuse (0.31% vs 0.57%; OR, 0.54; 95% CI, 0.43-0.68; P<0.001).
The authors concluded that GLP-1 RA use was consistently associated with lower CRC incidence across both study populations.
Clinical Implications
Patients with Crohn's disease and ulcerative colitis have a well-established increased risk of colorectal cancer due to chronic intestinal inflammation, making effective cancer prevention strategies an important clinical priority. While previous research has suggested that GLP-1 RAs may reduce CRC risk in broader populations, evidence in patients with IBD has been limited.
These findings indicate that GLP-1 RA therapy may offer benefits beyond glycemic control in patients with IBD, particularly those with concomitant T2DM. However, the study's retrospective observational design precludes conclusions about causality. Residual confounding and unmeasured factors may have influenced the observed association despite rigorous propensity score matching.
Prospective clinical studies and randomized investigations will be necessary to determine whether GLP-1 RAs directly reduce CRC risk and to clarify the biological mechanisms underlying the observed association. Until then, standard CRC surveillance recommendations for patients with IBD remain unchanged.
The study adds to the growing body of evidence suggesting that GLP-1 receptor agonists may have potential anticancer effects. If confirmed in prospective research, these findings could further strengthen the role of GLP-1 RAs in managing high-risk patients with IBD and type 2 diabetes while potentially improving long-term colorectal cancer outcomes.
Reference:
Ailawadi S, Murphy JE, Storandt MH, Mahipal A. GLP-1 receptor agonist use and colorectal cancer risk in patients with inflammatory bowel disease. J Clin Oncol. 2026; 44 (suppl 19; abstr 138). DOI: 10.1200/JCO.2026.44.19_suppl.138
