Reevaluating the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) vs aspirin for colorectal cancer prevention in type 2 diabetes.

e15690 Background: Recent studies suggest that aspirin and GLP-1RA may reduce the risk of colorectal cancer (CRC). A recent presentation reported a substantially greater primary preventive effect of GLP-1RA compared with aspirin, with an estimated 36% risk reduction. However, this analysis excluded patients using NSAIDs and other anti-diabetic medications, despite GLP-1RAs being predominantly prescribed for type 2 diabetes (T2D) and commonly used in combination with agents such as metformin. We therefore re-evaluated CRC risk among GLP-1RA and aspirin users with T2D, adjusting for background anti-diabetic therapies and other key covariates. Methods: We utilized the TriNetX Global Collaborative Network, a de-identified electronic medical record database encompassing over 160 institutions worldwide, to identify patients with T2D between 2010 and 2023. Two mutually exclusive cohorts were defined: patients using any GLP-1RA without aspirin (GLP-1RA cohort) and patients using aspirin without any GLP-1RA (aspirin cohort). Patients with a prior history of CRC or benign colorectal neoplasms were excluded. Propensity score matching was performed on demographics, comorbidities, laboratory values, including HbA1c, BMI, and medications, including background anti-diabetic therapies. The index date was defined as the first recorded use of GLP-1RA or aspirin. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CRC risk. Results: After PSM, 402,661 patients were included in each cohort. Baseline characteristics were well balanced, with a mean age of 57 years, 62% White, and 57% female. Anti-diabetic regimens were also well matched: 50% of patients in each cohort used metformin, 19% sulfonylureas, 11% SGLT2 inhibitors, 12% DPP-4 inhibitors, and 34% insulin. BMI remained higher in the GLP-1RA cohort compared with the aspirin cohort (36.1 vs 34.1) after matching. Mean follow-up was shorter in the GLP-1RA cohort (1,100 days) than in the aspirin cohort (1,530 days). CRC occurred in 0.2% (884/402,661) of patients in the GLP-1RA cohort and 0.3% (1,209/402,661) in the aspirin cohort; however, these crude incidence differences reflect unequal follow-up duration between cohorts. In Cox regression analysis accounting for time-to-event, there was no significant difference in CRC risk between cohorts (HR 1.018, 95% CI 0.932–1.112, p = 0.693). Results remained non-significant at 5-year (HR 1.003, 95% CI 0.912–1.104, p = 0.945) and 10-year follow-up (HR 0.971, 95% CI 0.890–1.059, p = 0.504). Conclusions: Among patients with T2D, when NSAID use and background hypoglycemic medications were not excluded and anti-diabetic therapies were matched, GLP-1RA use was not associated with greater CRC risk reduction compared with aspirin. Given the inherent limitations of retrospective analyses, prospective studies are warranted.