Abstract

Metformin, a widely-prescribed antihyperglycemic drug for the treatment of diabetes mellitus type 2 (DM-II), has been demonstrated to be antineoplastic in vivo and in vitro. However, various preclinical and epidemiological studies investigating the effects of metformin on lung cancer have obtained inconclusive results. The aim of the present study was to retrospectively investigate the effects of metformin, for the treatment of diabetes mellitus type 2 (DM-II), on the onset of lung cancer. In the present study, the pathological features of ten consecutive young age lung cancer cases, aged between 15 and 45 years old at the time of diagnosis and exhibiting existing primary DM, were investigated using the Mayo Clinic Lung Cancer Cohort database. Amongst this cohort, there were 2 cases of DM type 1 (DM-I) and 8 cases of DM-II. Of these patients, two exhibiting adenocarcinoma and DM-II had not been administered metformin; however, 1 patient exhibiting lymphoma and 4 patients with pulmonary neuroendocrine tumors (NETs) had been administered metformin at least 12 months prior to lung cancer diagnosis. The remaining 3 patients exhibiting NETs and DM-II had been treated with insulin therapy. The present study hypothesized that the high proportion of NETs observed in the cases of metformin-treated DM-II was unlikely to be a random event. It was suggested that metformin treatment was not effective in the prevention of pulmonary NETs, and that metformin may instead induce the occurrence of NETs via as yet unknown signaling pathways. The present hypothesis may potentially serve as a novel indicator for the requirement to monitor young patients with diabetes, who are being treated with metformin, for the occurrence of pulmonary NETs.

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