GLP-1 Receptor Agonists Reduce Colorectal Cancer Risk in IBD Populations

Data from a large retrospective cohort study to be presented at the 2026 American Society of Clinical Oncology (ASCO) Breakthrough Meeting showed that GLP-1 receptor agonist (GLP-1 RA) use was significantly associated with lower colorectal cancer incidence among patients with inflammatory bowel disease (IBD), including those with comorbid type 2 diabetes (T2D).^1,2

What were the key colorectal cancer findings in patients with IBD?

Among 69,221 propensity-matched patients with IBD, those who had received a GLP-1 RA had a 5-year colorectal cancer incidence of 0.2% compared with 0.42% in non-GLP-1 RA users (OR, 0.49), corresponding to a 51% reduction in odds of developing colorectal cancer. In a parallel matched cohort of 37,740 patients with both IBD and T2D, GLP-1 RA users had a 5-year colorectal cancer incidence of 0.31% vs 0.57% in non-users (OR, 0.54), representing a 46% reduction in odds. GLP-1 agents examined in the analysis included semaglutide (Wegovy), dulaglutide (Trulicity), tirzepatide (Zepbound), exenatide (Byetta), liraglutide (Saxenda), and lixisenatide (Lyxumia).

What was the design of this colorectal cancer risk study?

This retrospective cohort study drew on TriNetX, a US healthcare database encompassing more than 150 million patients. Investigators identified 1,137,300 patients with IBD, including 70,303 GLP-1 RA users and 1,066,997 non-users. After propensity matching for age, sex, race, and obesity, 69,221 patients were included in the primary analysis. A second cohort of 209,649 patients with both IBD and T2D, of whom 38,567 had received a GLP-1 RA, was matched similarly, yielding 37,740 patients for analysis.

“Patients with [IBD] and both [IBD] and [T2D] represent particularly high-risk populations for colorectal cancer. However, to our knowledge, this population has not been studied at a larger scale,” said presenting author Sarina Ailawadi, DO, from the Department of Medicine at Case Western Reserve University in Cleveland, Ohio, in the press release.¹

Why are patients with IBD at elevated risk for colorectal cancer?

IBD, which encompasses Crohn's disease and ulcerative colitis, is associated with chronic intestinal inflammation and widely regarded as a primary driver of colorectal carcinogenesis. Patients with IBD are approximately 6 times more likely to develop colorectal cancer than those without IBD. T2D independently elevates colorectal cancer risk, though the cumulative impact of both conditions had not previously been studied at scale. GLP-1 RAs are hypothesized to confer a cancer-risk benefit partly through anti-inflammatory mechanisms, in addition to their established effects on glycemic control and weight reduction.

Julie R. Gralow, MD, FACP, FASCO, chief medical officer and executive vice president of ASCO, said, “People with [IBD], including Crohn’s disease and ulcerative colitis, are known to have higher risk of developing colorectal cancer. This large population-based study found that people with [IBD] who received [GLP-1 RA] medications, either for diabetes or other reasons, had a lower incidence of developing colon cancer compared to those who did not receive those medications. This is promising data that supports the need for further studies evaluating whether GLP-1 receptor antagonists can reduce risk in this population at high risk for developing cancer.”¹

What are next steps for GLP-1 research in this population?

Ailawadi and colleagues plan to characterize the adverse effect profile of GLP-1 RAs, specifically in patients with IBD. Commonly reported GLP-1 adverse effects—including nausea, vomiting, constipation, and abdominal discomfort—substantially overlap with symptoms of an IBD flare, which may complicate safety monitoring and clinical assessment. The investigators noted that prospective studies are needed to confirm the protective benefit suggested by this retrospective analysis.

How has CancerNetwork® covered GLP-1 receptor agonists in oncology?

Earlier this year, CancerNetwork reported on a large real-world analysis that found that concurrent GLP-1 RA use was linked to significantly improved long-term survival and lower rates of immune-related adverse events in patients receiving immune checkpoint inhibitors.³ CancerNetwork also covered data associating GLP-1 RA use with a modest reduction in hormone receptor–positive/HER2-negative breast cancer incidence and improved overall survival in nondiabetic women with elevated body mass index.⁴

References

1. GLP-1s may reduce colorectal cancer risk in patients with inflammatory bowel disease. Press release. ASCO. June 22, 2026. Accessed June 24, 2026. https://tinyurl.com/39pykra4
2. 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. 2025;44(suppl 19):138. doi:10.1200/JCO.2026.44.19_suppl.138
3. Jajja S, Thukral J, Abdalla A, et al. The association of GLP-1 receptor agonist use with survival and immune-related adverse events in patients receiving immune checkpoint inhibitors: A multi-institutional real-world analysis. J Clin Oncol. 2026;44(suppl 16):11000. doi:10.1200/JCO.2026.44.16_suppl.11000
4. Shah Z, Hundal J, Afridi SS, et al. GLP-1 therapy and hormone receptor–positive breast cancer risk and survival: A real-world analysis. J Clin Oncol. 2026;44(suppl 16):10548. doi:10.1200/JCO.2026.44.16_suppl.10548