PURPOSE: The diabetes drugs metformin and TZDs may have a protective effect against the development or progression of lung cancer. A potential mechanism of this effect is through the activation of AMP-activated protein kinase (AMPK). Metformin directly activates, and TZDs indirectly activate, the AMPK pathway. When cells are faced with energy stresses AMPK functions to restore energy balance by inhibiting synthetic pathways and stimulating catabolic pathways. This function may serve to protect against lung cancer development or progression. The purpose of this study was to determine if diabetic patients who develop lung cancer and have been exposed to metformin or TZDs, have a different lung cancer presentation and course than diabetic patients who have not been exposed to these medications.
METHODS: The medical records of 157 diabetic patients who had a history of lung cancer were reviewed. Data collected included demographics, smoking history, diabetic medication use, and lung cancer characteristics (stage at presentation, histology, survival). Lung cancer characteristics were compared between the group that had been exposed to metformin and/or TZDs prior to their lung cancer diagnosis and those who had not received either of these medications prior to their lung cancer diagnosis.
RESULTS: There were no significant differences between the age, sex, and smoking histories of the group exposed to metformin or TZDs prior to their lung cancer diagnosis and the group who was not exposed. Those who were exposed had a lower chance of presenting with metastatic disease (20.0% vs. 42.4%, p=0.027). They were more likely to present with an adenocarcinoma and less likely to present with a small cell or squamous cell carcinoma (p=0.019). The HR for survival in the exposed group, after correction for stage, was 0.56 (p=0.056).
CONCLUSION: Diabetic patients with lung cancer who are previously exposed to metformin and/or TZDs are less likely to present with metastatic disease, more likely to present with an adenocarcinoma, and may survive longer.
CLINICAL IMPLICATIONS: The chemopreventive and treatment effects of these medications warrant additional study.
DISCLOSURE: Peter Mazzone, No Financial Disclosure Information; No Product/Research Disclosure Information