The effect of GLP-1 receptor agonists on outcomes in metastatic renal cell carcinoma patients undergoing immune checkpoint inhibitor therapy: A retrospective multi-institutional US cohort study.

4559 Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have played a pivotal role in the management of type 2 diabetes (T2DM). At the same time, immune checkpoint inhibitor (ICI) therapy remains one of the mainstay treatments for metastatic renal cell carcinoma (mRCC). There has been a scarcity of research on the effect of GLP-1 receptor agonists on ICI efficacy in cancer patients. This study presents the first real-world analysis of the effect of GLP-1 receptor agonists on outcomes in mRCC patients receiving ICI therapy. Methods: Data was retrospectively collected from TriNetX, a national electronic health record database with 120 million US patients from over 70 healthcare organizations, from 2012-2024. We included patients ≥ 18 years old with T2DM and mRCC who underwent ICI therapy. Patients were then stratified into two cohorts: on GLP-1 receptor agonists prior to ICI therapy and not on GLP-1 receptor agonists. Patients in each cohort were then 1:1 propensity score matched (PSM) based on age, sex, race, type of ICI therapy used, comorbidities, other diabetic medications and staging. 1 year outcomes for mortality, major adverse cardiovascular events (MACE) and various immune‐related adverse events (irAEs) were reported. Results: A total of 2378 patients were identified who met the inclusion criteria. 535 (22%) were in the GLP-1 receptor agonist cohort compared to 2378 (68%) in the non GLP-1 receptor agonist cohort. After 1:1 PSM, 497 patients were in each group. Among both cohorts, 66% were male, 77% white and the average age was about 65 years old. After conducting Cox proportional hazard analyses, GLP-1 receptor agonist use was associated with lower mortality (HR, 0.49 [95% CI: 0.37-0.64]). Moreover, GLP-1 receptor agonist use had lower rates of irAEs, including pneumonitis (HR, 0.61 [95% CI: 0.43-0.85]), hematological complications (HR, 0.78 [95% CI: 0.64-0.95]) and renal complications (HR, 0.67 [95% CI: 0.54-0.84]). There was no significant difference in MACE or other irAEs between the two cohorts. Conclusions: Analysis of one of the largest US based databases showed that the use of GLP-1 receptor agonist in T2DM patients with mRCC undergoing ICI therapy, is associated with better overall survival and lower irAES such as pneumonitis, hematological and renal complications. There was no significant difference in MACE. To our knowledge, this is the first study to identify the impact of GLP-1 receptor agonists on the outcomes of mRCC patients undergoing ICI therapy. Further prospective studies are needed to validate these findings and to identify the underlying mechanisms.