GLUCAGON-LIKE peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes and weight reduction, may offer significant benefits in improving outcomes for patients with non-small cell lung cancer (NSCLC), according to new clinical and preclinical evidence.
Researchers analyzed two clinical cohorts of overweight and obese patients with NSCLC to evaluate the effect of GLP-1RA use. In the surgical resection group of 1,177 patients, 71 who used GLP-1RAs experienced increased recurrence-free survival, with hazard ratios indicating a strong survival benefit compared with matched non-users. In a separate cohort of 300 patients receiving immune checkpoint inhibitors (ICIs), 10 GLP-1RA users showed improved overall and progression-free survival, suggesting potential synergy between GLP-1RAs and immunotherapy.
Preclinical experiments provided further insight, showing that GLP-1RA treatment significantly reduced tumor burden in obese mice but not in normal-weight counterparts. These effects were linked to alterations in leukocyte populations and gene expression within the tumor microenvironment, pathways known to be critical for tumor progression and immune response. Together, these findings point to obesity-specific mechanisms driving the anti-tumor effects of GLP-1RAs.
The study underscores the potential of GLP-1RAs as adjunctive therapy in lung cancer care, particularly for overweight and obese patients. By improving recurrence-free survival following surgery and enhancing responsiveness to immunotherapy, GLP-1RAs may represent a dual-action therapeutic option that integrates metabolic control with cancer-specific benefit. While the clinical cohorts were small, particularly in the immunotherapy arm, the convergence of human and animal data highlights a promising avenue for future investigation.
If validated in larger trials, the use of GLP-1RAs in oncology could provide physicians with a metabolic-immune strategy to improve outcomes in NSCLC, especially in populations where obesity complicates disease progression and treatment response.
Reference:
Pachimatla AG et al. Glucagon-like peptide-1 receptor agonism improves lung cancer outcomes and tumor growth control. JCI Insight. 2025;doi:10.1172/jci.insight.195484.
