Real world outcomes comparing the use of GLP-1 agonists in patients with renal cell carcinoma (RCC) and comorbid obesity: A propensity score matched analysis from Global Federated Health Research Network.

484 Background: Renal cell carcinoma (RCC) is the most common type of urogenital cancer. Lifestyle and metabolic risk factors seem to play an important role in this rising incidence. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with RCC and comorbid obesity. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with RCC and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, heart failure, ischemic stroke, chronic kidney disease (CKD), metabolic dysfunction-associated steatotic liver disease (MASLD), and need for hemodialysis. Results: We identified 2232 patients with RCC and obesity who received GLP-1 receptor agonists, and 13090 patients with RCC and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 2231 patients with similar baseline characteristics. Our analysis found that over 5 years, patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.493, 95% CI: 0.427 to 0.57, p-value < 0.001), myocardial infarction (Risk Difference: -2.239%, 95% CI: -3.836 to -0.642, p-value = 0.006), heart failure (Risk Difference: -4.213%, 95% CI: -6.876 to -1.551, p-value = 0.002), ischemic stroke (ischemic stroke: -2.111%, 95% CI: -3.44 to -0.781, p-value = 0.002), and CKD (Risk Difference: -8.526%, 95% CI: -11.441 to -5.611, p-value < 0.001). There was no statistically significant difference in the risk for MASLD and need for hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, heart failure, CKD and ischemic stroke. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.