A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia

Abstract

OBJECTIVE -Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucoseand lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.RESEARCH DESIGN AND METHODS -We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n ϭ 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n ϭ 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals.RESULTS -Triglyceride levels were reduced by 51.9 Ϯ 7.8 mg/dl with pioglitazone, but were increased by 13.1 Ϯ 7.8 mg/dl with rosiglitazone (P Ͻ 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 Ϯ 0.5 vs. 2.4 Ϯ 0.5 mg/dl; P Ͻ 0.001) and the increase in LDL cholesterol was less (12.3 Ϯ 1.6 vs. 21.3 Ϯ 1.6 mg/dl; P Ͻ 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P Ͻ 0.001). LDL particle size increased more with pioglitazone (P ϭ 0.005).CONCLUSIONS -Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size. Diabetes Care 28:1547-1554, 2005T wo core metabolic defects contribute to the development of type 2 diabetes: relative insulin insufficiency and insulin resistance. Approximately 92% of patients with type 2 diabetes demonstrate insulin resistance (1). Even in the absence of overt hyperglycemia, insulin resistance is associated with a cluster of abnormalities that increase the risk for cardiovascular disease (CVD), including dyslipidemia, increased expression of inflammatory markers, activation of procoagulants, hemodynamic changes, and endothelial dysfunction (2,3).The dyslipidemia associated with insulin resistance and type 2 diabetes is characterized by elevated triglycerides and decreased HDL cholesterol (4 -6). Although LDL cholesterol may not be elevated in type 2 diabetes, an increase in the proportion of small, dense, and potentially more atherogenic LDL cholesterol particles is observed (7). In addition to LDL cholesterol, elevated triglyceride levels and reduced HDL cholesterol levels are both risk factors for coronary heart disease (CHD) (8 -11). Compared with nondiabetic individuals, patients with type 2 diabetes have a two-to fourfold high...

PPAR-γ agonist rosiglitazone protects peritoneal membrane from dialysis fluid-induced damage

“…In fact, it has been shown that RSG administration to diabetic patients decreases the circulating levels of glycated hemoglobin. 54 The decrease of peritoneal AGEs in PD fluid instilled mice fits well with the observed reduction of MMT, fibrosis and angiogenesis, and with the preservation of the mesothelium in vivo. Furthermore, the better preservation of the mesothelium may also be explained by a direct effect of RSG on mesothelial cell survival, as witnessed in vitro by analyzing apoptosis.…”

n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet

“…These results are in accordance with the known hypolipidaemic effects of n-3 LC-PUFA [1] and rosiglitazone [25] in mice. Interest- ingly, in humans, only pioglitazone but not rosiglitazone exerted a hypolipidaemic effect [19], documenting that the hypolipidaemic effect of TZDs may be dissociated from their effect on insulin sensitivity [25]. The lowering of NEFA levels in mice subjected to various treatments could reflect several mechanisms, including adipose tissue lipolysis, re-esterification of NEFA in liver and adipose tissue, and stimulation of lipid oxidation in liver [14] and other organs [10] by n-3 LC-PUFA, as well as by TZDs [26,27].…”

“…On the other hand, PPAR-γ ligands [19] such as thiazolidinediones (TZDs) are the preferred therapeutic agents for insulin resistance in type 2 diabetic patients. However, TZDs like rosiglitazone and pioglitazone are also associated with unwanted side effects, such as oedema and weight gain [20], possible risk of heart failure [21] and bone loss [22].…”

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy

“…There is an increase in adiposity, largely subcutaneous, with some reduction in visceral fat shown in some studies. The TZDs either have a beneficial (pioglitazone) or neutral (rosiglitazone) effect on atherogenic lipid profiles [63,64]. Several meta-analyses have suggested a 30-40% relative increase in risk for myocardial infarction [65,66] with rosiglitazone.…”