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Glucagon-like peptide-1 receptor agonism improves lung cancer outcomes and tumor growth control

Akhil Goud Pachimatla1, Bailey Fitzgerald2, Joyce Ogidigo3

  • 1Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, New York, USA.

JCI Insight
|August 26, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise in improving non-small cell lung cancer (NSCLC) outcomes, particularly in obese patients. These drugs may also enhance immunotherapy effectiveness in advanced NSCLC.

Area of Science:

  • Oncology
  • Metabolic Disease
  • Immunology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for diabetes and obesity.
  • Emerging evidence suggests GLP-1RAs may reduce the incidence of various cancers.
  • The role of GLP-1RAs in non-small cell lung cancer (NSCLC) outcomes is under investigation.

Purpose of the Study:

  • To investigate the association between GLP-1RA use and NSCLC outcomes in overweight and obese patients.
  • To explore the mechanistic insights of GLP-1RA effects on NSCLC using mouse models.
  • To evaluate the combined efficacy of GLP-1RAs and immunotherapy in advanced NSCLC.

Main Methods:

  • Analysis of two clinical cohorts of overweight/obese NSCLC patients (surgical and ICI-treated) using propensity score matching.
  • Evaluation of clinical outcomes including recurrence-free survival and overall survival.
  • Preclinical studies in obese mouse models to assess tumor burden, leukocyte populations, and gene expression.

Main Results:

  • GLP-1RA use was linked to improved recurrence-free survival in overweight/obese NSCLC patients post-surgery.
  • In obese mice, GLP-1RA treatment reduced tumor burden and modulated immune cell profiles and gene expression.
  • Concurrent GLP-1RA and immunotherapy correlated with better overall and progression-free survival in advanced NSCLC patients.

Conclusions:

  • GLP-1RAs appear to improve lung cancer-specific outcomes and augment immunotherapy efficacy in the studied cohort.
  • Preclinical data suggest these benefits are obesity-dependent and involve immune modulation of the tumor microenvironment.
Keywords:
Clinical ResearchDrug therapyLung cancerObesityOncology

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