[Effects of thiazolidinediones on dyslipidemia in patients with type 2 diabetes. Are all equally vasoprotective?]

Abstract

Patients with type 2 diabetes face a high risk of cardiovascular morbidity and mortality. In these patients a whole cluster of cardiovascular risk factors is found, with insulin resistance being the most significant. Thiazolidinediones, in activating the peroxisome proliferator-activated receptor gamma, lower the insulin resistance. The two thiazolidinediones available at present, pioglitazone and rosiglitazone, do not differ in their effects on insulin resistance or glucose metabolism. They do, however, reveal very different effects on the dyslipidemia that is characteristic of diabetes, with elevated triglycerides, low high-density lipoprotein (HDL) and atherogenic small dense lipoprotein (LDL) cholesterol. Inter alia, data from a comparative study show that pioglitazone improves diabetic dyslipidemia more efficaciously than rosiglitazone. Despite similar effects on hyperglycemia (HbA1c reduction by 0.6% and 0.7%), both thiazolidinediones differ significantly in their effects on triglycerides (pioglitazone -51.9 mg/dl; rosiglitazone +13.1 mg/dl; p < 0.001), HDL cholesterol (pioglitazone +5.2 mg/dl; rosiglitazone +2.4 mg/dl; p < 0.001) and LDL cholesterol (pioglitazone +12.3 mg/dl; rosiglitazone +21.3 mg/dl; p < 0.001). LDL particle concentration was reduced with pioglitazone (n7.85%) and increased with rosiglitazone (+12%; p > 0.001). Only for pioglitazone the PROactive study, a major outcome trial, documented a significant reduction of cardiovascular outcomes. The principal secondary endpoint of death from any cause, nonfatal myocardial infarction (excluding silent myocardial infarction) or stroke was significantly reduced (16%; p = 0.027). The correlation of improved dyslipidemia, reconfirmed by PROactive, and cardiovascular prevention is yet to be resolved. However, as long as the vascular protective mechanism of pioglitazone is not conclusively resolved, findings may not be transmitted to other thiazolidinediones. For these substances, results from major outcome studies are to be required that prove a reduction of the cardiovascular risk.