Association of GLP-1 receptor agonist use with overall survival in patients with colorectal cancer and type 2 diabetes: A multicenter real-world study.

e15556 Background: Colorectal cancer (CRC) is closely linked to obesity and type 2 diabetes mellitus (T2DM), conditions associated with worse oncologic outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control, but their association with survival after CRC diagnosis remains unclear. We evaluated the association between GLP-1 RA exposure and overall survival (OS) in patients with CRC and T2DM. Methods: We performed a retrospective cohort study using the TriNetX research network (2010–2024). Adults (≥18 years) with incident CRC and T2DM were identified. Patients receiving GLP-1 RAs were compared with patients receiving other antidiabetic therapies, including metformin, insulin and insulin analogues, sodium–glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Propensity score matching (1:1) was performed using demographics, comorbidities, medications, cancer characteristics, and baseline laboratory values. Overall survival was assessed using Kaplan–Meier methods and Cox proportional hazards models. Results: After matching, 1,485 CRC patients remained in each group. In the matched cohort, the mean age was 67.7 years; 55% were male and 45% female. Most patients had colon cancer (77%), and the cohort was predominantly White (68%). Baseline metabolic profiles and comorbidities were well-balanced between groups (Table 1). Among non–GLP-1 RA users, the most common antidiabetic therapies included metformin (54%), followed by insulin or insulin analogues (35%), SGLT2 inhibitors (27%), sulfonylureas (22%), and DPP-4 inhibitors (7%). GLP-1 RA use was associated with improved overall survival. One-year OS was 92.7% in the GLP-1 RA group versus 90.2% in the non–GLP-1 group (log-rank p = 0.017; HR 0.73, 95% CI 0.56–0.95). At the longest duration of sufficient follow-up, 5-year OS was 78.6% versus 72.0%, respectively (log-rank p = 0.0003; HR 0.72, 95% CI 0.60–0.86). Conclusions: In this large multicenter real-world cohort of patients with colorectal cancer and type 2 diabetes, GLP-1 receptor agonist use was associated with significantly improved short- and long-term overall survival. These findings support further investigation of GLP-1 RAs as potential prognostic modifiers in colorectal cancer. Baseline characteristics (Matched Cohort). Characteristic GLP-1 RA (n=1,485) Non–GLP-1 Therapy (n=1,485) Demographics Age, mean ± SD (years) 67.7 ± 10.9 70.1 ± 11.1 Male sex, % 55.0 54.6 White, % 68.2 68.2 African American, % 15.1 14.0 Hispanic, % 9.8 9.2 Metabolic Profile Body mass index, mean ± SD (kg/m²) 33.7 ± 8.0 33.0 ± 7.7 Hemoglobin A1c, mean ± SD (%) 7.54 ± 1.78 7.33 ± 1.73 Comorbidities Hypertension, % 71.0 71.0 Cardiovascular disease, % 19.7 19.9 Chronic kidney disease, % 15.1 15.2 Chronic Liver disease, % 8.9 8.9 COPD, % 7.3 7.3