Diabetes drug acts as chemopreventive in smokers

Metformin, a biguanide antidiabetic drug administered orally, could play a critical role in controlling, and possibly preventing, lung cancer in at-risk patients. Animal studies conducted at NCI demonstrated that treating mice with metformin reduced lung tumor volume by about 50%.

Metformin decreases levels of insulin-like growth factor-1 (IGF-1) and circulating insulin, which is important in patients with type II diabetes. Emerging research suggests metformin may inhibit tumor growth as well.

"Metformin is being studied in many cancers," said the study coinvestigator Regan Memmott, an MD/PhD candidate at the University of Cincinnati. Her group's results "provide rationale for a clinical prevention trial with metformin in heavy smokers who are at high risk to develop lung cancer." They also support clinical testing of metformin as a chemopreventive agent, she said.

Study leader Phillip A. Dennis, MD, PhD, senior investigator in the medical oncology branch of NCI, treated mice with metformin for 13 weeks following exposure to a nicotine-derived nitrosamine (NNK), a carcinogen that is a known promoter of lung tumorigenesis.

When given orally, metformin was well tolerated and reduced tumor burden by 40% to 50%, the group reported, adding that the levels of metformin reached in mice would be readily achievable in humans.

The group also evaluated the effects of metformin on a series of biomarkers for lung tumorigenesis and found that it inhibited mammalian target of rapamycin (mTOR).

This effect was even more profound when metformin was administered to mice by injection, reducing lung tumor burden by 72%, according to Ms. Memmott's research (AACR 2010 abstract 2928).