The risk of coronary heart disease in type 2 diabetic patients exposed to thiazolidinediones compared to metformin and sulfonylurea therapy

Purpose -
To evaluate whether the risk of coronary heart disease (CHD) differs among adult diabetic patients treated with thiazolidinediones (TZDs) and similar patients treated with combined oral metformin and sulfonylurea (M + S) therapy.

Methods -
We conducted a retrospective cohort study involving 25 140 diabetic patients aged 18 and older who had at least one pharmacy claim for a TZD or combined M + S therapy between 1 January 1999 and 30 June 2002. We used propensity score matching to adjust for observable differences between initiators of combined M + S therapy and TZD initiators. The data were analyzed in two ways: first based on the original matched groups, as balanced, without accounting for switching to another medication during follow-up, and second based on actual antidiabetic drug use during follow-up, as treated. Cox proportional hazards regression and multivariable Poisson regression were performed to compare the risk of CHD events.

Results -
In the as balanced analysis, the risk for CHD among TZD users relative to combination drug users was close to the null value (adjusted hazard ratio: 1.02, 95% confidence intervals (CI): 0.87-1.20). In the as treated analysis, the risk of CHD was similar for periods of current use of TZDs compared to periods of non-use (incidence rate ratio: 1.10, 95%CI: 0.96-1.25).

Conclusions -
These results do not suggest a cardioprotective or deleterious effects of TZDs compared with combined M + S oral therapy on the short-term CHD event risk in persons with type 2 diabetes after accounting for the greater baseline CHD risk in TZD initiators.