Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System

BMC Med. 2007 Jun 21;5:17. doi: 10.1186/1741-7015-5-17.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Distribution
  • Causality
  • Comorbidity
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology*
  • New Hampshire / epidemiology
  • New York / epidemiology
  • Pioglitazone
  • Prevalence
  • Rosiglitazone
  • Sex Distribution
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use*
  • Vermont / epidemiology

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Pioglitazone