The effect of metformin and thiazolidinedione use on lung cancer in diabetics

Abstract

BackgroundMetformin and the thiazolidinediones (TZDs) may have a protective effect against the development of lung cancer.MethodsPatients with diabetes mellitus (DM) were identified from the electronic medical records of the Cleveland Clinic. Diabetics with lung cancer were identified then verified by direct review of their records. Control subjects were matched with cancer subjects 1:1 by date of birth, sex, and smoking history. The frequency and duration of diabetic medication use was compared between the groups. The cancer characteristics were compared between those with lung cancer who had and had not been using metformin and/or a TZD.Results93,939 patients were identified as having DM. 522 lung cancers in 507 patients were confirmed. The matched control group was more likely to have used metformin and/or a TZD (61.0% vs. 41.2%, p < 0.001 for any use; 55.5% vs. 24.6%, p < 0.001 for >24 months vs. 0–12 months). In the group with lung cancer, those who had used metformin alone had a different histology distribution than those who received neither metformin nor a TZD, were more likely to present with metastatic disease (40.8% vs. 28.2%, p = 0.013), and had a shorter survival from the time of diagnosis (HR 1.47, p < 0.005).ConclusionsThe use of metformin and/or the TZDs is associated with a lower likelihood of developing lung cancer in diabetic patients. Diabetics who develop lung cancer while receiving metformin may have a more aggressive cancer phenotype.

Metformin use and survival from lung cancer: A population-based cohort study

“…Inconsistent with our findings, two previous studies reported significant reductions in all-cause mortality in users of metformin before [13] or after [14] lung cancer diagnosis. A further study reported a shorter overall survival in pre-diagnostic metformin users compared to non-users [12]. Unlike our investigation, previous studies did not investigate dosedependent relationships [12][13][14] and metformin use after diagnosis was time-fixed [14], thus potentially introducing immortal time bias.…”

“…A further study reported a shorter overall survival in pre-diagnostic metformin users compared to non-users [12]. Unlike our investigation, previous studies did not investigate dosedependent relationships [12][13][14] and metformin use after diagnosis was time-fixed [14], thus potentially introducing immortal time bias. Moreover, results from studies investigating allcause mortality could be reflective of non-cancer mortality.…”

“…Some, but not all [8] have reported improvements in progressionfree survival [9] and disease-free survival [10,11] but these investigations were limited by small sample sizes [8][9][10][11], drug exposure determined at limited numbers of time-points [8][9][10][11] and a lack of adjustment for important baseline patient characteristics [9]. Other studies have investigated metformin use and overall survival [12][13][14], but these results could reflect mortality from non-cancer causes.…”

Survival of Patients with Stage IV Lung Cancer with Diabetes Treated with Metformin

“…There have been few publications examining metformin's influence on lung cancer risk (31)(32)(33)(34). These studies show varying results regarding metformin and risk for developing lung cancer and lung cancer prognosis.…”

“…These studies show varying results regarding metformin and risk for developing lung cancer and lung cancer prognosis. In a retrospective casecontrol study, Mazzone and colleagues (31) found that metformin was associated with a more aggressive lung cancer phenotype and worse prognosis. Conversely, two observational studies, a small Chinese study with patients with lung cancer and a larger UK study that included many cancer types, showed that metformin was associated with improved survival in patients with lung cancer (17,18).…”