Study Led by Roswell Park’s Dr. Sai Yendamuri Finds GLP-1 Receptor Agonists Improve Lung Cancer Outcomes

Lung cancer patients who take medications called GLP-1 receptor agonists — commonly prescribed for weight loss and diabetes management — fare better than those who don’t, according to research led by Sai Yendamuri, MD, MBA, FACS, Chair of Thoracic Surgery at Roswell Park Comprehensive Cancer Center, and Joseph Barbi, PhD, Assistant Professor, Department of Immunology. Results of the study, which involved investigators from both Roswell Park and the Columbia University Irving Medical Center, appear in JCI Insight.

Amid growing evidence that people who take GLP-1 receptor agonists, also known as GLP-1RAs or GLP 1 inhibitors, have a lower incidence of several different types of cancer, Dr. Yendamuri, senior author of the study, and his colleagues explored the medications’ effects on patients diagnosed with non-small cell lung cancer (NSCLC). They conducted two retrospective analyses of overweight or obese patients with NSCLC. One dataset included 1,177 patients treated with surgical resection, of whom 71 took a GLP-1RA drug. The second comprised 300 patients treated with a type of immunotherapy called an immune checkpoint inhibitor; of those, 10 also took a GLP-1RA drug.

The team’s data revealed that GLP-1RA use was associated with longer recurrence-free survival in the surgical group, while in the second group, concurrent use of GLP-1RA and immune checkpoint inhibitors was associated with improved overall and progression-free survival. In the same study, GLP-1RA in preclinical models of lung cancer reduced the tumor burden in obese but not normal-weight subjects. Drug-induced changes in the tumor microenvironment that coincided with those effects suggest that the benefits of GLP-1RAs may stem from their ability to favorably reprogram anti-tumor immunity.

It’s estimated that more than 4% of the U.S. population now use GLP-1RAs, which are FDA-approved and marketed under several brand names, including Ozempic, Wegovy, Zepbound and Mounjaro. This class of medications may therefore present a fast-track opportunity to improve the effectiveness of promising immunotherapies and expand the treatment options available for NSCLC, but more research is needed.

Bailey Fitzgerald, MD, Assistant Professor of Oncology in Roswell Park’s Department of Medicine, and Akhil Goud Pachimatla, MD, former postdoctoral student in Thoracic Surgery, are co-first authors of the study.

The research was funded by a grant from the National Institutes of Health/National Cancer Institute and a generous donation from George Duke.