Metformin may reduce lung cancer risk for nonsmokers with diabetes

Use of metformin appeared to offer a protective effect against lung cancer among nonsmokers with diabetes, according to results of a retrospective study.

“Our study suggests that metformin use is not associated with lung cancer risk in all patients with diabetes, but that such risk might differ by smoking history,” Lori C. Sakoda, PhD, MPH, research scientist at the Kaiser Permanente Division of Research in Oakland, Calif., told HemOnc Today. “Although intriguing, this finding must be confirmed by other large, well-conducted studies.”

Metformin, frequently prescribed as a first-line treatment for type 2 diabetes, has shown signs of chemotherapeutic properties for the treatment of cancer in certain laboratory settings.

Results of lab studies on mice and other observational studies suggest metformin also may help prevent certain cancers, but human studies have yielded conflicting evidence, according to study background.

Sakoda and colleagues retrospectively evaluated data on 47,351 individuals with diabetes. All were aged at least 40 years and completed health-related surveys between 1994 and 1996.

About 46% of patients were ever-users of metformin, meaning they filled at least two prescriptions for the agent within a 6-month period.

During 15 years of follow-up, 1.6% of patients were diagnosed with lung cancer. Of those,

10.7% were considered never-smokers and 27.2% were considered current smokers.

Metformin use was not associated with reduced risk for lung cancer in the entire cohort (HR = 1.02; 95% CI, 0.85-1.22).

However, patients who had never smoked demonstrated a 43% reduction in risk for lung cancer (HR = 0.57; 95% CI, 0.33-0.99). This risk seemed to decrease further with prolonged use of metformin. Nonsmokers who used metformin for 5 years or longer demonstrated a 52% reduced risk for lung cancer (HR = 0.54; 95% CI, 0.22-1.35).

Metformin use for 5 or more years was associated with a 31% decrease (HR = 0.69; 95% CI, 0.40-1.17) in risk for lung adenocarcinoma — the most common form of lung cancer in nonsmokers — and an 82% increased risk (HR = 1.82; 95% CI, 0.85-3.91) for small cell carcinoma, a type of cancer often diagnosed in smokers. However, neither of those findings were statistically significant.

When researchers compared patients who took the highest doses of metformin with never-users, they observed even greater differences in risk for adenocarcinoma (HR = 0.61; 95% CI, 0.28-1.3) and small cell carcinoma (HR = 3.11; 95% CI, 1.22-7.95).

Results showed no clear associations between metformin use and lung cancer risk based on tumor stage or gender, researchers wrote.

“Our results suggesting that the risk associated with metformin might differ by smoking history were unexpected,” Sakoda said. “Additional large, well-conducted studies are needed to clarify whether metformin may be used to prevent lung or other cancers, particularly in specific subpopulations such as nonsmokers.” – by Anthony SanFilippo

For more information:

Lori C. Sakoda, PhD, MPH, can be reached at Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612; email: lori.sakoda@kp.org.

Disclosure: Sakoda reports no relevant financial disclosures. Two researchers report research funding from Genentech, Sanofi and Takeda