The association of GLP-1 receptor agonist use with survival and immune-related adverse events in patients receiving immune checkpoint inhibitors: A multi-institutional real-world analysis.

Abstract

11000 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed in patients with cancer for metabolic comorbidities and weight management. However, their impact on outcomes in patients receiving immune checkpoint inhibitors (ICIs) remains poorly characterized. We evaluated the association between concurrent GLP-1 RA use and survival and immune-related adverse events (irAEs) in a large real-world oncology population. Methods: We conducted a federated electronic health record–based cohort study using the TriNetX Research Network (113 healthcare organizations). Adult patients with solid and hematologic malignancies treated with PD-1/PD-L1 or CTLA-4 inhibitors were identified. Patients were stratified by exposure to GLP-1 RAs. Propensity score matching was performed to balance demographics, comorbidities, and baseline clinical characteristics. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare overall survival at 3 and 5 years. Incidence of irAEs, including neutropenia and pyrexia, was assessed using risk and odds ratios. Results: A total of 3,807 patients receiving ICIs with concurrent GLP-1 RAs were matched to 173,423 patients receiving ICIs without GLP-1 RAs. At 3 years, GLP-1 RA exposure was associated with improved survival (hazard ratio [HR] 0.69, 95% CI 0.64–0.75; log-rank p<0.001). This survival advantage persisted at 5 years (HR 0.71, 95% CI 0.65–0.76; log-rank p<0.001). Survival probability at the end of follow-up was higher in the GLP-1 RA cohort across both time horizons. No statistically significant survival benefit was seen at the 1-year end point, (HR 0.65, 95% CI 0.59-0.71; log-rank p=0.521). GLP-1 RA use was associated with a lower incidence of selected irAEs. At 3 years, neutropenia occurred in 5.7% of GLP-1 RA users versus 6.5% of non-users (OR 0.87, 95% CI 0.71–1.06), and pyrexia was significantly reduced (risk difference −2.5%, OR 0.73, 95% CI 0.61–0.87). Similar trends were observed at 5 years, with numerically lower neutropenia rates in the GLP-1 RA cohort (OR 0.84, 95% CI 0.68–1.02). Conclusions: In this large real-world analysis, concurrent GLP-1 RA use in patients receiving ICIs was associated with significantly improved long-term survival and a reduced burden of selected immune-related adverse events. These findings suggest a potential synergistic or protective effect of GLP-1 RAs in the immunotherapy setting and warrant prospective investigation to clarify underlying mechanisms and clinical implications. Outcome 5-Year GLP-1 n/N (%) 5-Year No GLP-1 n/N (%) Death 1091/3411 (32) 1545/3410 (45) Malaise & Fatigue 552/2190 (25) 628/2160 (29) Sepsis 444/3016 (15) 521/2964 (18) Cachexia 119/3395 (4) 179/3368 (5) Pneumonia 405/2811 (14) 494/2747 (18)