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In patients with diabetes, the use of metformin did not reduce the risk of lung cancer overall, but the risk was reduced among patients who never smoked.
Diabetic patients who had no history of smoking had a lower risk of lung cancer if they were treated with metformin for their diabetes. The results of this retrospective cohort study were published in Cancer Prevention Research.
“Metformin use was not associated with lung cancer risk when we looked at all patients with diabetes. However, our results suggest that risk might differ by smoking history, with metformin decreasing risk among nonsmokers and increasing risk among current smokers,” said Lori Sakoda, MPH, PhD, a research scientist at Kaiser Permanente Division of Research in Oakland, California, in a statement.
Both preclinical and observational studies have suggested that metformin, typically the first-line therapy for diabetes, may help prevent cancer. But, prior studies analyzing the link between metformin and lung cancer risk have produced mixed results, which may reflect biases in the methods employed in these studies, according to the authors of the new study.
Sakoda and colleagues analyzed health-related surveys completed by 47,351 diabetic patients, age 40 and over, being treated for their diabetes. The incidence of lung cancer among this cohort was followed until 2012. Fifty-four percent of the cohort was men, and 46% had a history of taking metformin for their diabetes.
During the 15-year follow-up, 747 patients were diagnosed with lung cancer. Of those with lung cancer, 203 were current smokers and 80 were never smokers.
The use of metformin was not associated with lower risk of lung cancer overall. However, the risk of lung cancer was 43% lower among diabetic patients who used metformin and who had never smoked. The risk decreased with longer metformin use. Those who used metformin for 5 or more years had a 52% lower risk of lung cancer, but the decrease was not statistically significant.
The use of metformin for 5 or more years was linked with a 31% decrease in the risk of adenocarcinoma of the lung-the most common type of lung cancer diagnosed among nonsmokers. The risk of small-cell carcinoma, a type of lung cancer usually diagnosed in smokers, increased by 82% in those who took metformin for 5 or more years. However, these associations were not statistically significant.
Metformin users tended to be younger, with a mean age of 59.3 years compared with 65 years for patients who did not take metformin.
These results suggested that the risk of lung cancer associated with metformin use varies depending on smoking history.
Metformin has been shown to suppress lung tumor growth in obese mice with hyperinsulinemia by increasing insulin sensitivity. Metformin has also been shown to influence the AMP-activated protein kinase pathway, which is thought to be relevant in tumorigenesis. But, the exact mechanism of how metformin may be antitumorigenic is not clear.
The current study is limited because relatively few metformin-using patients in the cohort developed lung cancer, reducing the significance of risk estimates.
“Future studies of metformin use and lung cancer risk should be conducted in larger, well-characterized cohorts of persons with diabetes over an extended period of follow-up, accounting for time-related and other potential biases,” concluded the study authors.
The study was funded by the National Institutes of Health.