Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System.
BACKGROUND
Peroxisome proliferator-activated receptors (PPARs) have emerged as important drug targets for diabetes. Drugs that activate PPARgamma, such as the thiazolidinediones (TZDs), are widely used for treatment of Type 2 diabetes mellitus. PPARgamma signaling could also play an anti-neoplastic role in several in vitro models, although conflicting results are reported from in vivo models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes.


METHODS
A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs.


RESULTS
In a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides), age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, P = 0.04). This association was particularly strong among patients using rosiglitazone (OR = 1.89, P = 0.02), and among women (OR = 2.07, P = 0.01).


CONCLUSIONS
These data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.
Ramos-Nino
Maria E
ME
University of Vermont, Department of Pathology, Vermont 05405, USA. Maria.Ramos@uvm.edu
MacLean
Charles D
CD
Littenberg
Benjamin
B
D017677:Age Distribution; D015984:Causality; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D009513:New Hampshire / Q000453:epidemiology; D009518:New York / Q000453:epidemiology; D000077205:Pioglitazone; D015995:Prevalence; D000077154:Rosiglitazone; D017678:Sex Distribution; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use*; D014707:Vermont / Q000453:epidemiology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone