Combination thiazolidinedione and fibrate effect on high-density lipoprotein cholesterol (HDL-C) concentration in a Veterans Affairs patient population

Background Type 2 diabetes mellitus (T2DM) is a coronary heart disease (CHD) risk equivalent warranting aggressive management of dyslipidemia and tight glycemic control. Recent reports demonstrate a paradoxic decrease in high-density lipoprotein cholesterol (HDL-C) with thiazolidinedione (TZD) and fibrate combination therapy. Objective Evaluate change in HDL-C from start of combination therapy to 1 year and assess the proportion, characteristics, and regimens of patients who developed a ≥20% decrease in HDL-C from baseline. Methods Patients with T2DM treated concurrently with a combination of TZD and fibrate were identified through retrospective query from a Veterans Affairs medical center database. HDL-C was recorded for 1 year after patients started combination therapy. Logistic regression analysis was performed to determine any predictors of HDL-C change. Results A total of 322 patients were included in the analysis. There was no significant differences in mean ± standard deviation HDL-C from baseline to end point (36.8 ± 8.5 to 40.3 ± 11.8 mg/dL; P = 0.097). There was a subset of patients identified (13%; n=43) on combination therapy who experienced a ≥20% reduction in HDL-C. Of these patients, a decrease in HDL-C was more likely to occur with fenofibrate-based regimens (odds ratio 3.08, 95% confidence interval 1.22 to 7.75; P = 0.018). There was a trend toward more of these patients in this subset to have the combination of rosiglitazone and fenofibrate in their profiles (odds ratio 2.82, 95% confidence interval 0.98 to 8.0; P = 0.064). Conclusion Our study demonstrated that a subset of patients with T2DM experienced a paradoxic decrease in HDL-C when taking a fibrate and TZD combination.