The effect of exposure to thiazolidinediones on the development of head-and-neck cancer in patients with diabetes mellitus

Background: Thiazolidinediones (TZDs) are proliferator-activated receptor-γ (PPAR-γ) ligands with a variety of metabolic activities approved for the treatment of type 2 diabetes mellitus. In addition to being potent hypoglycemic agents, they are recognized through in-vitro studies as having antiproliferative activity. This study was conducted to explore the impact of TZD exposures on the development of head-and-neck cancer. Methods: A retrospective cohort analysis was conducted on subjects attending 10 Veterans Affairs medical centers comprising Veterans Integrated Services Network 16 (VISN-16). Data were collected from the VISN-16 database created from the electronic patient charts. Male diabetics who were eligible to be prescribed TZDs were followed for the development of head-and-neck cancer. Head-and-neck cancers were identified by International Statistical Classification of Diseases 9 (ICD 9) codes; exposures to TZDs and other antidiabetic agents were determined from pharmacy dispensing records. Results: A total of 130,406 subjects who met the study criteria were followed for a total of 571,237 person-years, during which time 911 head-and-neck cancers developed. There was a significant reduction in the incidence of head-and-neck cancers among subjects exposed to TZDs after adjusting for other antidiabetic agents, race, age, body mass index (BMI), and glycosylated hemoglobin [hemoglobin A1C (HbA1C)] (hazard ratio 0.43, confidence interval 0.21–0.89; p = 0.023). Conclusion: A statistically significant reduction was noted in the incidence of head-and-neck cancers among male diabetic veterans exposed to TZDs. These data warrant further investigation.