Comparative effects of rosiglitazone and pioglitazone on fasting and postprandial low-density lipoprotein size and subclasses in patients with Type 2 diabetes

Abstract

Objective: To assess the effects of pioglitazone and rosiglitazone on fasting and postprandial low-density lipoprotein (LDL) size and subclasses in patients with Type 2 diabetes. Research design and methods: Nine Type 2 diabetic patients (age 61 ± 10 years, body mass index 30 ± 5 kg/m2, glycosylated hemoglobin [HbA1c] 7.5 ± 0.5%) were randomized in a crossover trial to rosiglitazone 4 mg b.i.d. or pioglitazone 45 mg/day for 12 weeks with an 8-week wash-out period. LDL size and subclasses were determined by non-denaturing polyacrylamide gradient gel electrophoresis. A standardized breakfast was served and variables were assessed after 3 and 6 h. Results: HbA1c, insulin sensitivity (as assessed by the homeostasis model assessment) and LDL size and subclasses did not differ before treatments. Rosiglitazone and pioglitazone resulted in a similar improvement in HbA1c and insulin sensitivity. Fasting total cholesterol increased more after rosiglitazone compared with pioglitazone (p = 0.04), whereas triglycerides decreased after pioglitazone and increased after rosiglitazone (p = 0.004). Fasting LDL size similarly increased after both treatments, mainly due to increased LDL-I particles. Pioglitazone resulted in a more prominent LDL-IIA subfraction compared with rosiglitazone (p = 0.03). After 3 h, pioglitazone lead to increased LDL-IIB (p = 0.01) and decreased LDL-IVB (p = 0.05), however, after 6 h no significant changes were found. Conclusions: Pioglitazone was more effective than rosiglitazone in increasing larger LDL concentrations (in both fasting and postprandial status) as well as in reducing levels of atherogenic small, dense particles (in postprandial status only). Whether or not these findings differentially affect the atherogenic process and the clinical endpoints such as cardiovascular events remains to be determined.