GLP-1 receptor agonist therapy and cancer risk and mortality in patients with moderate CKD: A national matched cohort study of 58,000 patients.

10583 Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been associated with reduced mortality in patients with Type 2 Diabetes Mellitus (T2DM) and may lower cancer risk. However, the impact of GLP-1 RAs on cancer incidence and mortality in patients with chronic kidney disease (CKD) remains understudied. Thus, in this study we evaluated whether GLP-1 RA use modifies cancer risk and mortality in a contemporary national cohort of patients with moderate CKD. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults aged 18–90 years with T2DM and newly diagnosed stage-3 CKD between January 2015 and February 2025. Patients with prior malignant neoplasms or end-stage renal disease were excluded. Exposure was defined as a prescription for a GLP-1 RA within 90 days before CKD diagnosis; controls had no documented GLP-1 RA use. Outcomes were evaluated beginning 90 days after the index CKD diagnosis to reduce reverse-causation and immortal-time bias. Our primary outcome was any malignant neoplasm. Our secondary outcomes were site-specific malignant neoplasms (colorectal, lung, liver, kidney, pancreatic, breast, and prostate) as well as all-cause mortality. We performed 1:1 propensity score matching balancing demographics, comorbidities, laboratory values (hemoglobin A1c and estimated glomerular filtration rate), and cardiometabolic medications. After matching, we calculated absolute risks, risk differences, hazard ratios, risk ratios, and 95% confidence intervals. Statistical significance was defined as p < 0.05. Results: After matching, 28,948 patients remained in each group. GLP-1 RA use was associated with significantly lower all-cause mortality (8.6% vs 15.0%; HR 0.57; 95% CI, 0.546-0.599; p < 0.001). Overall malignant neoplasm incidence was significantly lower with GLP-1 RA use (7.0% vs 7.7%; RR 0.90; p < 0.001). Among site-specific malignancies, the GLP-1 RA group demonstrated lower incidence of lung cancer (0.5% vs 0.8%; RR 0.56; p < 0.001), colorectal cancer (0.5% vs 0.7%; RR 0.74; p = 0.006), and liver cancer (0.3% vs 0.4%; RR 0.63; p = 0.001). Pancreatic cancer (0.2% vs 0.3%; RR 0.89; p = 0.46), kidney cancer (0.5% vs 0.6%; RR 0.98; p = 0.87), prostate cancer (1.1% vs 1.0%; RR 1.08; p = 0.32), and breast cancer (0.7% vs 0.7%; RR 1.11; p = 0.30) did not differ significantly based on GLP-1 RA receipt. Conclusions: In patients with T2DM and stage-3 CKD, GLP-1 RA therapy was associated with substantially lower mortality and reduced incidence of several major malignancies, particularly lung, colorectal, and hepatocellular cancers. These findings highlight a potential role for GLP-1–mediated metabolic modulation in cancer prevention among high-risk populations. Prospective studies are warranted to clarify mechanisms and confirm these observations.