Diabetes Drug May Help Fight Lung Cancer in Overweight Patients: Study

Metformin may improve immune responses in lung cancer patients with obesity. Read about the implications for future clinical trials.

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A common diabetes medication may offer new hope for overweight patients battling lung cancer.

Researchers have found that metformin, a decades-old drug used to control blood sugar, could improve immunotherapy outcomes and extend recurrence-free survival in lung cancer patients carrying extra weight.

The study findings suggest obesity as a potential driver of cancer, and patients who lose their extra weight may have a better prognosis.

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Lung cancer is currently the leading cause of American cancer deaths, and nearly 235,000 new cases of the illness are diagnosed each year. An estimated 125,070 people will die from the disease in 2024, according to data from the American Cancer Society.

“Our study ... suggests that metformin may improve the outlook for overweight and obese lung cancer patients by correcting the detrimental effects that the conditions have on the anti-tumor immune response,” Joseph Barbi, assistant professor of oncology in Roswell Park’s Department of Immunology and co-senior author of the study, told The Epoch Times.

He noted that more research is needed to test the effects of metformin in combination with other cancer drugs in overweight cancer patients.

Anti-Cancer Benefits of Metformin

Scientists at Roswell Park Comprehensive Cancer Center in Buffalo, New York, hypothesized that the anti-cancer benefits of metformin might be particularly evident in lung cancer patients who are overweight or obese. This theory is supported by two decades of evidence linking metformin to slowed cancer progression.

Researchers were intrigued by past clinical trials, which often involved patients of normal weight and did not demonstrate clear anti-cancer benefits. They proposed that including predominantly normal-weight patients might have obscured more robust evidence regarding the drug’s effects in specific populations, particularly those who are overweight or obese.

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For their new study, published in the Journal of the National Cancer Institute, researchers analyzed data from two distinct patient cohorts. The first included 511 overweight patients with a body mass index (BMI) of 25 or higher and 232 patients with a BMI of less than 25, which is considered healthy. All participants underwent surgery.

In the second cohort, the focus was on the impact of metformin on progression-free survival among 284 overweight patients compared to 184 non-overweight patients who received immunotherapy, a type of cancer-fighting drug.

“Our work shows that the anticancer effect of metformin is active only in the context of obesity,” Dr. Sai Yendamuri, chief strategy officer and chair of thoracic surgery at Roswell Park Comprehensive Cancer Center and lead study author, said in a statement. “We observed longer recurrence-free survival in overweight patients who took metformin and underwent surgery.”

Metformin can help cancer patients, especially those who are overweight, in three ways:

• Reduced Cancer Recurrence: For overweight people who had surgery to remove part of a lung (lobectomy), metformin was linked to a lower chance of cancer coming back.
• Slowed Tumor Growth: Metformin slowed tumor growth in overweight mice by affecting the immune system.
• Improved Immunotherapy: Metformin was more effective in treating cancer in overweight mice and human patients when combined with immunotherapy.

“Obesity is known to negatively affect the immune system in ways that can be expected to undermine effective anti-tumor immunity and promote poor outcomes,” Barbi said. “In earlier work, we associated visceral or central obesity with aggressive disease and immune dysfunction in lung cancer patients and preclinical cancer models.”

Mechanism of Action

In preclinical studies, metformin has been shown to slow tumor growth and reverse immune suppression caused by obesity. Combining metformin with an immune checkpoint inhibitor led to enhanced control of tumor growth, although these effects were primarily observed in obese patients.

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“In obese or overweight patients, metformin appears to shift the balance between immune-suppressing mechanisms and those that activate tumor-killing processes,” Barbi said in the statement.

Previous research has shown that metformin users generally have a reduced risk of the potentially fatal disease, and a study conducted with mice found that metformin can also prevent tobacco use-related lung tumor growth.

Findings Lead to New Clinical Trial

The researchers aim to inspire future studies by highlighting the potential of metformin-containing treatment regimens to improve clinical outcomes in at-risk populations.

Based on these findings, the research team has designed a phase 2 clinical trial, the second phase of clinical research that evaluates a new medical treatment, such as a drug or therapy. The trial is designed to assess metformin’s potential in preventing lung cancer in high-risk overweight or obese individuals. According to Roswell Park researchers, the center is one of only three sites in the United States and Canada offering this trial and is funded by the National Cancer Institute.

Barbi said that with increasing proportions of lung cancer patients being classified as overweight or obese, understanding the effect of excess weight and body fat on disease progression and immune function is important for effective lung cancer treatment and the design of new therapies for a changing patient pool.

“While our study was focused on lung cancer,” he said, “it is possible that metformin may have similar context-specific effects in other malignancies.”

Since the changes triggered by the drug in obese lung cancer models can be expected to generally improve anti-tumor immune responses, Barbi noted that “further studies should explore this possibility.”