A recent study led by Dr. Sai Yendamuri at Roswell Park Comprehensive Cancer Center indicates that metformin, a widely used drug for type 2 diabetes, may enhance the efficacy of immunotherapy in treating lung cancer, specifically in overweight or obese patients. The findings, published in the Journal of the National Cancer Institute, suggest that metformin's anti-cancer benefits are most pronounced in individuals with a body mass index (BMI) of 25 or higher.
Obesity-Dependent Anti-Cancer Effect
The research team analyzed data from 511 non-small cell lung cancer (NSCLC) patients with a BMI of 25 or higher and 232 patients with a BMI below 25, all of whom underwent surgery. Additionally, they evaluated the impact of metformin on progression-free survival in 284 overweight and 184 non-overweight NSCLC patients treated with immune checkpoint inhibitors. The results demonstrated that overweight patients who took metformin experienced longer recurrence-free survival following surgery.
Dr. Yendamuri stated, "Our work shows that the anticancer effect of metformin is active only in the context of obesity. We observed longer recurrence-free survival in overweight patients who took metformin and underwent surgery."
Preclinical Evidence
Preclinical studies in animal models further supported these findings. Metformin was shown to slow tumor growth and reverse obesity-driven suppression of the immune system. The combination of metformin and an anti-PD-1 antibody therapy (an immune checkpoint inhibitor) resulted in even greater tumor growth control, but this effect was primarily observed in obese models.
Immunological Mechanisms
According to Dr. Joseph Barbi, Assistant Professor of Oncology at Roswell Park, metformin appears to shift the balance between immune-suppressing mechanisms and tumor-killing processes in overweight or obese patients. This suggests that metformin may enhance the immune system's ability to target and eliminate cancer cells in this specific population.
Future Directions
Based on these findings, Drs. Yendamuri and Barbi are planning a phase 2 clinical trial (NCT04931017) to assess metformin's potential in preventing lung cancer in overweight or obese individuals at high risk for the disease. "By calling attention to the potential of metformin-containing treatment regimens to improve clinical outcomes for obese and overweight patients, we hope to inspire future studies," Dr. Barbi noted.
Metformin's Potential
Lung cancer remains the leading cause of cancer death in the United States, with approximately 235,000 new cases diagnosed each year and over 125,000 deaths annually, according to the American Cancer Society. Repurposing metformin, a drug with a long-established safety record and affordability, could offer a significant advantage in combating lung cancer, particularly in the growing population of overweight and obese individuals.
Dr. Yendamuri emphasized, "Metformin has been used for 30 years and has a long record of safety – and it’s one of the most widely accessible and affordable drugs of any kind. If we can repurpose it to fight cancer, that’s very exciting."
