Use of GLP-1 receptor agonist was significantly associated with a lower 5-year incidence of colorectal cancer among patients with inflammatory bowel disease (IBD), including those with concomitant type 2 diabetes, according to findings presented at the 2026 ASCO Breakthrough Meeting in Singapore.¹

In a matched retrospective analysis using the TriNetX database, the 5-year incidence of colorectal cancer was 0.20% among GLP-1 receptor agonist users vs 0.43% among nonusers in the overall IBD cohort, corresponding to 51% lower odds of colorectal cancer. Among patients with both IBD and type 2 diabetes, the 5-year incidence was 0.31% among GLP-1 receptor agonist users vs 0.57% among nonusers, corresponding to 46% lower odds.

“Patients with inflammatory bowel disease and both inflammatory bowel disease and type 2 diabetes represent particularly high-risk populations for colorectal cancer. However, to our knowledge, this population has not been studied at a larger scale,” said lead study author Sarina Ailawadi, DO, of Case Western Reserve University and University Hospitals in Cleveland. “We found that GLP-1 use was beneficial in patients with IBD and reduced their risk of developing colorectal cancer. Future prospective studies will be important to further analyze its potential benefit.”

A High-Risk Population

GLP-1 receptor agonists have changed the treatment landscape for type 2 diabetes and obesity. They have also drawn increasing interest in oncology as researchers examine whether their effects on weight, insulin signaling, systemic inflammation, and other metabolic pathways may have implications for cancer risk and outcomes.

IBD, including Crohn’s disease and ulcerative colitis, is a known risk factor for colorectal cancer. Type 2 diabetes is also associated with an increased risk of colorectal cancer. During a press briefing ahead of the meeting, Dr. Ailawadi noted that prior studies have suggested an approximately 36% to 41% lower risk of colorectal cancer with GLP-1 receptor agonist use; however, the impact of these agents in patients with IBD had not been established.

In this study, investigators evaluated the association between GLP-1 receptor agonist use and colorectal cancer incidence in two high-risk populations: patients with IBD and those with both IBD and type 2 diabetes.

Study Design

The investigators conducted a retrospective cohort study using TriNetX, a U.S. health-care database that includes more than 150 million patients. ICD-10 codes were used to identify adults with preexisting IBD, including Crohn’s disease and ulcerative colitis, and to stratify them according to GLP-1 receptor agonist use.

Patients were excluded if they had a diagnosis of colorectal cancer, prior GLP-1 receptor agonist use, or prior total or partial colectomy before the study period, which spanned 2015 to 2025.

The GLP-1 receptor agonists included in the analysis were semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, and lixisenatide.

The overall IBD cohort comprised 1,137,300 patients, including 70,303 GLP-1 receptor agonist users and 1,066,997 nonusers. The IBD/type 2 diabetes cohort comprised 209,649 patients, including 38,567 GLP-1 receptor agonist users and 171,082 nonusers.

Propensity score matching was performed to create comparable treatment and control groups and reduce confounding. Matching variables included demographic factors, tobacco and alcohol use, hypertension, hyperlipidemia, obesity, IBD subtype, steroid use, immunosuppressive therapy (including biologics), and other type 2 diabetes medications.

After matching, the overall IBD analysis included 69,221 GLP-1 receptor agonist users and 69,221 matched nonusers. The IBD/type 2 diabetes analysis included 37,740 GLP-1 receptor agonist users and 37,740 matched nonusers.

Lower Colorectal Cancer Incidence in Both Cohorts

In the matched IBD cohort, GLP-1 receptor agonist use was significantly associated with a lower 5-year incidence of colorectal cancer: 0.20% among GLP-1 receptor agonist users vs 0.43% among nonusers (odds ratio [OR] = 0.49, P < .001).

A similar association was observed among patients with both IBD and type 2 diabetes. In this cohort, the 5-year incidence of colorectal cancer was 0.31% among GLP-1 receptor agonist users vs 0.57% among nonusers (OR = 0.54, P < .001).

“We found that there was significantly lower odds of developing colorectal cancer in patients who used GLP-1s, in both the patients with IBD and patients with IBD and type 2 diabetes,” Dr. Ailawadi reported during the press briefing.

Possible Mechanisms

The study was not designed to establish a mechanism, but the investigators discussed several biologically plausible explanations that warrant further research. Obesity, insulin resistance, type 2 diabetes, and chronic inflammation may contribute to colorectal cancer development through pathways involving epithelial proliferation, oxidative stress, and adenoma formation.

GLP-1 receptor agonists are associated with sustained weight loss, decreased insulin and insulin-like growth factor 1 signaling, and reduced systemic inflammation. Dr. Ailawadi said these pathways may help explain the observed association with lower colorectal cancer incidence, although prospective studies are needed to determine whether GLP-1 receptor agonists have a protective effect in this population.

The researchers also plan to evaluate the side effects of GLP-1 receptor agonists in patients with IBD. Common adverse effects of these agents, including nausea, vomiting, constipation, abdominal discomfort, and decreased appetite, may overlap with symptoms of IBD flares, making tolerability and clinical interpretation particularly important in this population.

Caution on Causality

Julie R. Gralow, MD, FACP, FASCO, ASCO Chief Medical Officer and Executive Vice President, said during the press briefing that the study adds to a growing body of research on GLP-1 receptor agonists and cancer, but she emphasized that the current evidence remains preliminary.

“We’re certainly seeing exciting signals for research that suggests that GLP-1 drugs may play an important role in cancer prevention and cancer outcomes,” Dr. Gralow said. “But these signals are from primarily observational studies, and they’re not proof of cause and effect.”

Julie R. Gralow, MD, FACP, FASCO

She noted that it remains too early to determine whether GLP-1 receptor agonists should be incorporated into cancer prevention or treatment strategies.

“It’s a bit too early to say if and how these drugs should be used in cancer care, because there’s still a lot that we don’t know and we need to find out,” Dr. Gralow said. “Before we can recommend if these drugs should be used for the prevention or treatment of cancer, we need more evidence from randomized clinical trials to provide gold-standard evidence that would change clinical practice.”

Dr. Gralow also emphasized the importance of this question for oncology, given the established connections between obesity, metabolic health, lifestyle factors, and cancer risk.

“This is a very important area of study in oncology, because of what we already understand about how obesity, metabolic, and lifestyle factors can affect cancer,” Dr. Gralow said. “Fortunately, the findings to date are encouraging, including the findings from this study, and create a very compelling case for investing in the research needed to help get the answers.”

Disclosure: Dr. Ailawadi and Dr. Gralow reported no relevant financial relationships. No funding sources were reported for the study.

REFERENCE

1. Ailawadi S, Murphy JE, Storandt MH: GLP-1 receptor agonist use and colorectal cancer risk in patients with inflammatory bowel disease. 2026 ASCO Breakthrough Meeting; Singapore. Abstract 138. Presented June 25, 2026.