Diabetes, Metformin, and Lung Cancer: Retrospective Study of the Korean NHIS-HEALS Database

Metformin is the first option in managing type 2 diabetes mellitus (DM) and has pleotropic effects. We studied the incidence of lung cancer in patients who received metformin therapy. This study was retrospectively designed and based on the Korean National Health Insurance Service–National Health Screening Cohort to determine whether metformin reduces lung cancer risk in the diabetic population. At baseline, all participants were 40 to 69 years old and were categorized into 3 groups: metformin nonrecipients with DM, metformin recipients with DM, and the nondiabetic group. A total of 336,168 individuals were included in the final analysis (314,291 nondiabetic individuals, 8806 metformin recipients, and 13,071 metformin nonrecipients). The study median follow-up period was 12.86 years. The estimated cumulative lung cancer incidence of metformin nonrecipients, metformin recipients, and the nondiabetic group was 1.80%, 1.97%, and 1.24% in men and 1.87%, 0.61%, and 0.41% in women, respectively (P < .05). Compared to metformin nonrecipients, the hazard ratios (95% confidence intervals) for lung cancer incidence of metformin recipients and the nondiabetic group were 1.287 (0.979-1.691) and 0.835 (0.684-1.019) in men and 0.664 (0.374-1.177) and 0.553 (0.359-0.890) in women, respectively. The hazard ratios (95% confidence intervals) were statistically significant in male ever smokers (0.784 [0.627-0.979]) and female nonsmokers (0.498 [0.320-0.774]) after stratification according to smoking status. Metformin therapy did not reduce lung cancer incidence in the diabetic population. However, individuals without DM were at a lower risk of lung cancer, especially in male ever smokers and female nonsmokers. Metformin therapy provides pleotropic effects in addition to glycemic control. We studied lung cancer incidence in a retrospective study including 336,168 individuals and with a median study duration of 12.86 years. Metformin receipt did not reduce lung cancer incidence. However, individuals without diabetes were at a lower risk of lung cancer, especially in male ever smokers and female nonsmokers.