Evaluation of the impact of cardiovascular safety concerns of thiazolidinediones on the utilization of oral antidiabetic drugs

The overall objective of this study was to evaluate the impact of cardiovascular safety concerns on the utilization of the thiazolidinediones (TZDs), pioglitazone and rosiglitazone, and other oral antidiabetic drugs. In May 2007, a meta-analysis was published that found a potential increased risk of myocardial infarction (MI) associated with TZDs, particularly with rosiglitazone. A two-year retrospective study of patients diagnosed with type 2 diabetes (ICD9 250.xx) using prescription and medical databases from the Scott & White Health System (SWHS) was conducted. Patients aged 18 or older who were continuously enrolled with SWHS from 2006 to 2008 and had high adherence (Medication Adherence Ratio ≥80%) for either pioglitazone or rosiglitazone during the pre-safety warning period (May 2006- April 2007) were included. Patients were followed through the post-safety warning period (May 2007 - October 2008) or occurrence of event (discontinuation of index TZD drug). Patients who discontinued their index TZD drug by April 2008 were identified if they had a prescription filled for a new oral antidiabetic drugs (OADs), and followed until October 2008 or occurrence of event (discontinuation of new OAD). Cox proportional hazards models were used to assess the rate of and time to discontinuation of index TZD and new OAD with adjustment of age, gender and Charlson Comorbidity Index (CCI). A total of 531 patients (58 percent male; mean age [SD] = 61 [9.1] years) were included in the final analysis, 255 and 276 patients in the rosiglitazone and pioglitazone groups, respectively. The rate of discontinuation for the pioglitazone and rosiglitazone groups began to separate within 90 days of the index event (meta-analysis published in May 2007). In the pioglitazone group, the rate of discontinuation was significantly lower than in the rosiglitazone group ( HR = 0.56; 95% CI = 0.47, 0.67). A total of 21 patients did not experience discontinuation of their index medication. Among patients receiving a new OAD after discontinuing their index TZD (N = 95 rosiglitazone and N = 33 pioglitazone patients), there was no statistical significant in the rate of discontinuing their new OAD between the rosiglitazone and pioglitazone groups (HR = 0.98; 95% CI = 0.61, 1.59). However, patients who received metformin/sulfonylurea combinations had a lower rate of discontinuation compared to patients who received sulfonylureas (HR = 0.38; 94% CI = 0.21, 0.66). The analysis showed the cardiovascular safety concern of TZDs had a significant impact on the utilization of oral antidiabetic drug utilization.