Efficacy GLP-1 agonists, SGLT-2 inhibitors and other glucose-lowering medications on cardiorenal outcomes in patients with diabetes and cancer on immune checkpoint therapy.

11174 Background: Treatment with Immune checkpoint inhibitors (ICI) therapy has improved survival in multiple malignancies. However, patients with type 2 diabetes (T2D) and cancer receiving ICI are at heightened risk for adverse cardiorenal outcomes. Emerging evidence suggests that Glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) confer cardiorenal benefits in T2D. However, their impact among patients with T2D and cancer remains unclear. Hence, we aimed to evaluate the effectiveness of GLP-1RA, SGLT-2i, and other glucose-lowering therapies in reducing adverse cardiorenal events. Methods: A retrospective cohort study was conducted using the TriNetX. Adult patients with T2D and cancer treated with ICI (anti-PD1, anti-PDL1, or anti-CTLA4) between 2017 and 2024 were included. Patients were stratified into three groups based on therapy: GLP-1RA, SGLT-2i, and other second or third line medications. We performed 1:1 propensity score matching(PSM) to adjust for confounding factors, including demographics, comorbidities, cancer type, and medications. The primary outcomes were major adverse cardiovascular events(MACE), heart failure(HF) and cerebrovascular events(CVE)) and secondary outcome was of end-stage renal diseases (ESRD), the need for dialysis and all-cause mortality. Hazard ratios(HR) for outcomes were calculated using Cox proportional hazard models. Sensitivity analysis assessed statistical robustness. Results: We identified 6212 patients on GLP-1RA, 7068 on SGLT-2i, and 24693 on other second- or third-line medications. After PSM, 5381 patients were included in the GLP-1RA vs. SGLT-2i cohorts. There were no significant differences in cardiorenal outcomes between the two groups. However, all-cause mortality was significantly lower for GLP-1RA (HR 0.88). In the comparison of GLP-1RA vs. other glucose-lowering medications, 6206 patients were matched. GLP-1RA were associated with significantly lower rates of HF, MACE, CVE, ESRD and mortality (HR 0.74). Similarly, for SGLT-2is vs. other glucose-lowering medications, 7,069 patients were matched. SGLT-2i demonstrated lower rates of adverse outcomes, particularly HF and ESRD (HR 0.63). Subgroup analysis revealed consistent benefits across cancer types, with pronounced effects in renal and lung cancer. Conclusions: GLP-1RA and SGLT-2i significantly reduce cardiorenal risks in patients with T2D and cancer on ICIs. However, GLP-1RA provided a modest survival advantage over SGLT-2is. These results underscore the importance of individualized therapeutic strategies prioritizing GLP-1RA and SGLT-2is in this high-risk population to improve cardiorenal outcomes and survival. Further studies are warranted to validate these findings and explore underlying mechanisms.