Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study

Abstract

Prior studies found that thiazolidinediones (TZDs) might have tumour-suppressor activity mediated through cell-cycle arrest, induction of apoptosis and inhibition of cell invasion. The main objective of this study was to investigate the effects of TZDs on the risk of cancer among patients with type 2 diabetes mellitus (DM). Patients diagnosed with DM between 1 January 1998 and 31 December 2002 were identified from the Longitudinal Health Insurance Database (LHID) within the Taiwan National Health Insurance (NHI) programme. Using Cox regression models, we assessed the association between prescribed TZDs and cancer risk, TZDs' dose effect and the association between TZDs and specific cancer types. Hazard ratios (HR) were adjusted for potential confounders (age, gender, income, Charlson score index, metformin and insulin use). The adjusted HRs for those prescribed TZD were 0·74 (95% CI 0·43-1·26, P=0·27), 0·39 (95% CI 0·33-0·45, P<0·001) and 0·49 (95% CI 0·27-0·89, P=0·02), respectively, relative to non-DM patients, DM patients prescribed other anti-DM drugs besides TZDs and DM patients not prescribed any anti-DM drugs. In addition, the effects of TZDs were shown to be significantly dose dependent (P for trend<0·001). The risk of breast, brain, colorectal, ear-nose-throat, kidney, liver, lung, lymphatic, prostate, stomach, and uterus cancer was significantly lower in those prescribed TZDs. The results showed a decrease in cancer risk in diabetic patients using TZD, and the association was dose dependent.