Metformin May Benefit Obese Individuals with Lung Cancer, Study Finds

Can a low-cost diabetes medication help improve survival for overweight and obese individuals with lung cancer? New research suggests that metformin, a drug commonly used to manage blood glucose levels, may hold the key. Published in the Journal of the National Cancer Institute, the study shows that metformin could significantly enhance immunotherapy outcomes and improve recurrence-free survival in this high-risk group.

Any boost metformin might give to cancer treatment would likely be cost effective because it is so inexpensive. A month’s supply of 30 tablets costs approximately $10.

Despite early promising results from animal studies, clinical trials exploring metformin’s role in lung cancer treatment have shown mixed results. While some studies suggest benefits when combined with immune checkpoint inhibitors, such as Keytruda (pembrolizumab), others have found no such effect. However, some of these studies did not specifically focus on body mass index (BMI) or excluded individuals with obesity, a group that may benefit the most.

Obesity is a growing concern in the U.S., with the Centers for Disease Control and Prevention (CDC) reporting that 40.3% of adults are obese, emphasizing the need for better solutions tailored to overweight and obese individuals in cancer care.

The retrospective study, led by Sai Yendamuri, M.D., M.B.A., chair of thoracic surgery at Roswell Park Comprehensive Cancer Center in Buffalo, New York, specifically focused on this group of patients with non-small cell lung cancer (NSCLC). By narrowing their research to overweight and obese individuals, the team found that metformin might offer benefits that previous trials overlooked.

“Our work shows that the anticancer effect of metformin is active only in the context of obesity,” Yendamuri said in a news release.

The researchers analyzed data from two cohorts with NSCLC: one cohort of 511 patients who had a BMI of 25 or higher, and another with 232 patients who had a BMI under 25. Both groups underwent lobectomy (a type of lung surgery). They found that metformin use was linked to a significant increase in recurrence-free survival among overweight patients. Specifically, the hazard ratio (HR) for recurrence was 0.47, indicating nearly a 50% reduction in risk for those taking metformin.

The team also examined how metformin affected patients receiving immunotherapy. They analyzed progression-free survival data from 284 overweight/obese patients and 184 non-overweight patients treated with immune checkpoint inhibitors. They found that overweight/obese patients who received metformin alongside their immunotherapy had a 40% better chance of survival without disease progression (HR of 0.60).

The researchers also conducted experiments in animal models to explore possible anticancer mechanisms. They observed that metformin not only slowed tumor growth but also reversed obesity-related immune suppression in mice. When combined with immune checkpoint inhibitors, metformin further enhanced tumor control, reinforcing the idea that the drug’s effects are most pronounced in obese individuals. Metformin seems “to shift the balance between immune-suppressing mechanisms and those that activate tumor-killing processes,” Yendamuri and his co-authors said.

Metformin’s affordability makes it even more promising. An Rx for metformin 500 milligrams taken twice daily costs between $4 and $11 per month, according to GoodRx. With its accessibility and affordability, metformin could potentially become a powerful tool in the fight against lung cancer, especially for those most at risk.

“Metformin has been used for 30 years and has a long record of safety,” Yendamuri said in the press release. “If we can repurpose it to fight cancer, that’s very exciting.”

The next step for the research team is a phase 2 clinical trial looking at metformin’s potential to prevent lung cancer in high-risk overweight or obese individuals. The trial, funded by the National Cancer Institute, is being conducted at Roswell Park and two other centers in the U.S. and Canada.