Metformin may improve immunotherapy efficacy in obese lung cancer patients: Study

A new study published in the Journal of the National Cancer Institute found that metformin which is frequently used to regulate blood glucose levels in diabetic patients may enhance the benefits of immunotherapy and increase recurrence-free survival in overweight or obese lung cancer patients. Clinical results raised questions about its potential as a treatment for individuals with non-small cell lung cancer (NSCLC). Thus, Randall Smith and his colleagues postulated that individuals with non-small cell lung cancer who are overweight or obese would benefit from taking metformin.

This study used complimentary mouse models and retrospectively examined 2 clinical cohorts. The effect of metformin on clinical outcomes was assessed in one cohort of NSCLC patients who had lobectomies and were overweight (≥25 kg/m2, n = 511) or non-overweight (<25 kg/m2, n = 232). The impact of metformin on progression-free survival following immune checkpoint inhibitors in overweight (n = 284) versus non-overweight (n = 184) non-small cell lung cancer patients was investigated in another cohort. Lung cancer models were used to evaluate the effects of metformin on tumor growth, antitumor immunity, and immune checkpoint inhibitor responsiveness in obese and normal-weight mice.

After a lobectomy, metformin is linked to a higher recurrence-free survival rate in overweight patients. Also, it reversed many pathways of immune suppression exacerbated by obesity and corrected increased tumor development in diet-induced obese mice models in a lymphocyte-specific manner.

Programmed cell death 1 blocking in conjunction with metformin correlate with progression-free survival, and it was more successful in reducing tumor burden in fat mice in overweight individuals receiving immunotherapy. This phase 2 clinical research assessed the ability of the drug to prevent lung cancer in overweight or obese individuals who are at high risk for the illness, based on their preclinical and clinical data.

One of the most commonly available and reasonably priced medications of any sort, metformin has been in use for 30 years and has a lengthy history of safety. Metformin may increase the effectiveness of immunotherapy in this expanding demographic and improve lung cancer-specific clinical outcomes in individuals who are fat or overweight. Overall, this study clarifies the underlying immunological phenomena and finds obesity as a possible predictive biomarker of metformin's anticancer and immunotherapy-enhancing effects in lung cancer.

Reference:

Smith, R. J., Jr., Zollo, R., Kalvapudi, S., Vedire, Y., Pachimatla, A. G., Petrucci, C., Shaller, G., Washington, D., Rr, V., Sass, S. N., Srinivasan, A., Kannisto, E., Bawek, S., Jain, P., Rosario, S., Barbi, J., & Yendamuri, S. (2024). Obesity-Specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin. In JNCI: Journal of the National Cancer Institute. Oxford University Press (OUP). https://doi.org/10.1093/jnci/djae295