P2134 - Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) Use Reduces Risk of Early-Onset Colorectal Cancer in Patients with Type 2 Diabetes-Mellitus (T2DM)

Award: Presidential Poster Award

Temitope Olasehinde, MD¹, Gregory Cooper, MD², Jaime A. Perez, PhD^3
1University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH; ²Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH; ³University Hospitals Clinical Research Center, Cleveland, OH

Introduction: GLP-1RAs are currently utilized for the management of T2DM and obesity — two important risk factors for colorectal cancer development. Emerging literature has shown that GLP-1RAs are associated with a reduced risk of late-onset colorectal cancer (LO-CRC) in patients with T2DM. However, this effect has yet to be demonstrated for early-onset colorectal cancer (EO-CRC) — which has seen an alarming increase in incidence and has a greater association with T2DM and obesity compared to LO-CRC. We sought to examine the impact of GLP-1RA use on EO-CRC risk utilizing a large population-based database.

Methods: We performed a retrospective cohort study using a large federated de-identified health research network, TriNetX. We identified patients (age < 50 years) with a diagnosis of T2DM who were subsequently prescribed antidiabetic medications and had no prior CRC diagnosis. Within this population, we stratified patients into 2 cohorts based on first-time GLP-1RA use. We further performed subanalysis based on GLP-1RA use and the presence of obesity. We investigated the outcome of the first diagnosis of EO-CRC after GLP-1RA prescription. Propensity score matching was performed to balance cohorts. Differences between cohorts were calculated using t-test, chi-square/Fisher's exact test.

Results: We found a total of 1,815,788 patients with T2DM. Among them, 247,463 patients were in the GLP-1 cohort, whereas 1,568,325 were in the no GLP-1 cohort. After propensity score matching, both cohorts had 77,688 patients in each group. Compared to their no GLP-1 counterparts, the GLP-1 cohort was more likely to be older (44.21 ± 9.74 vs 36.45 ± 11.14, p< 0.001), female (56.3% vs 50.9%, p< 0.001), White (54.3% vs 53.4%, p< 0.001), non-Hispanic/Latino (65.1% vs 57.1%, p< 0.001), greater comorbidities (p< 0.001), and higher BMI (36.78 ± 7.03 vs 30.62 ± 8.48, p< 0.001) (Table 1). For the primary analysis, the GLP-1 cohort had significantly lower odds of developing EO-CRC (0.4% vs 0.7%, p< 0.001) compared to the no GLP-1 cohort (Figure 1A). In the subanalysis, the GLP+obese cohort had significantly lower odds of developing EO-CRC compared to the non-GLP+obese cohort (Figure 1B).

Discussion: This is the first large study to demonstrate that GLP-1RAs decrease the risk of developing EO-CRC in patients with T2DM regardless of weight. Future randomized controlled studies are needed to validate these findings, which may have significant implications for CRC prevention in younger patients.



Disclosures:


Temitope Olasehinde, MD¹, Gregory Cooper, MD², Jaime A. Perez, PhD³. P2134 - Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) Use Reduces Risk of Early-Onset Colorectal Cancer in Patients with Type 2 Diabetes-Mellitus (T2DM), ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.