Glucagon-like peptide-1 receptor agonist use in lung cancer patients receiving immune checkpoint inhibitors: A real-world study.

8598 Background: Immune checkpoint inhibitors (ICI) have become a cornerstone of treatment for lung cancer. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have been associated with improved outcomes in cancer patients in prior studies; however, their impact on outcomes among lung cancer patients receiving immunotherapy remains limited. Methods: We conducted a retrospective cohort study using the TriNetX real-world data platform. Adult patients with lung cancer treated with ICIs, including PD-1, PD-L1, or CTLA-4 inhibitors, were included. Patients were stratified based on exposure to GLP-1 RA. Propensity score matching (1:1) was performed to balance baseline demographics and comorbidities, including type 2 diabetes mellitus and body mass index. Primary outcomes included all-cause mortality, intensive care unit (ICU) admission, and hospitalization. Secondary outcomes included immune-related pneumonitis, colitis/enteritis, cachexia, and major adverse cardiovascular events (MACE). Results: After matching, 2,013 patients were included in each group, with a median follow-up of 372 days in the GLP-1 RA group and 383 days in the non-GLP-1 RA group. Mean age was 66.8 and 67.2 years, respectively, and approximately 50% of patients were male. Most patients were White (77.2% vs 71.8%), followed by Black (14.1% vs 14.0%) and Asian (2.1% vs 1.8%). GLP-1 RA use was associated with a significantly lower all-cause mortality rate compared with non-use (35.7% vs. 53.4%; p < 0.0001), with a hazard ratio of 0.65 (95% CI, 0.59–0.71). Significant reductions were also observed in ICU admissions (22.8% vs 29.0%; p = 0.0001), hospitalizations (64.1% vs 71.8%; p = 0.0001), pneumonitis (5.2% vs 6.8%; p = 0.0457), and MACE (19.9% vs 25.3%; p = 0.0026). No significant differences were observed in colitis/enteritis (9.3% vs 9.4%; p = 0.9704) or cachexia (8.0% vs 9.8%; p = 0.0650). In a subgroup analysis of lung cancer patients not receiving ICI, GLP-1 RA use was similarly associated with lower mortality, ICU admission, hospitalization, and MACE, without differences in immune-related toxicities. Conclusions: GLP-1 RA use among lung cancer patients was associated with improved survival, reduced healthcare utilization, and fewer selected adverse events in patients receiving ICI therapy. These associations likely reflect established metabolic and cardiovascular benefits of GLP-1 RA and may also involve antitumor mechanisms suggested in prior studies. Residual confounding related to healthcare access and socioeconomic factors cannot be fully excluded and should be considered when interpreting these findings. Prospective studies are warranted to validate these observations and clarify underlying biological mechanisms.