Observational studies suggest that cancer incidence is lower in patients with type 2 diabetes treated with metformin, relative to patients treated with other diabetes medications. The few studies to examine metformin use in relation to lung cancer risk, however, have produced inconsistent results. To clarify this relationship, we conducted a retrospective cohort study of 50,722 adults aged 40 years or older included in the Kaiser Permanente Northern California Diabetes Registry, who completed a mailed survey administered in 1994 to 1996 on health-related traits and behaviors. All prescribed diabetes medications were identified for each patient from pharmacy records. Patients were followed for lung cancer from 1997 to 2009, with a median follow-up of 8.1 years. Using Cox regression, with age as the time scale, rate ratios (RR) and 95% confidence intervals (CI) were calculated to estimate risk of lung cancer associated with new use of metformin, adjusted for sex, race/ethnicity, smoking status, income, education level, diabetes duration, baseline measures of hemoglobin A1c and creatinine, and ever use of other types of diabetes medications. Measures of metformin use, along with ever use for each type of diabetes medication, were modeled as time-dependent variables. During 389,887 person-years of follow-up, 685 patients were diagnosed with lung cancer. The adjusted RR for ever use of metformin was 0.95 (95% CI, 0.79-1.14). For duration of metformin use, the adjusted RRs for <2.0, 2.0-4.9, and 5.0+ years were 1.01 (95% CI, 0.80-1.28), 0.94 (95% CI, 0.73-1.22), and 0.86 (95% CI, 0.63-1.18), respectively. In analyses stratified by smoking status, the adjusted RRs for ever use of metformin were 0.98 (95% CI, 0.79-1.21) in ever smokers and 0.59 (95% CI, 0.34-1.01) in never smokers. However, in never smokers, the number of users diagnosed with lung cancer was relatively small, and no dose-response decrease in risk with increasing duration of metformin use was found; the corresponding adjusted RRs for <2.0, 2.0-4.9, and 5.0+ years of metformin use were 0.52 (95% CI, 0.23-1.16), 0.58 (95% CI, 0.26-1.26), and 0.70 (95% CI, 0.31-1.58), respectively. Our results suggest that metformin use is not associated with lung cancer risk in former or current smokers with diabetes. Additional research is needed to determine whether metformin use might alter lung cancer risk in never smokers with diabetes.

Citation Format: Lori C. Sakoda, Ninah S. Achacoso, Charles P. Quesenberry, Tiffany Peng, Samantha F. Ehrlich, Assiamira Ferrara, Laurel A. Habel. Metformin use and risk of lung cancer in patients with diabetes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2274. doi:10.1158/1538-7445.AM2013-2274