The Long-term Effects of Rosiglitazone on Serum Lipid Concentrations
The Long-term Effects of Rosiglitazone on Serum Lipid Concentrations
Objective: Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight.
Design: Open labelled clinical study.
Patients and Measurements: We prospectively evaluated fasting serum glucose, haemoglobin A1c (HbA1c), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients.
Results: TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained.
Conclusions: HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.
Thiazolidinediones (TZDs) are oral antihyperglycaemic agents that reduce insulin resistance (IR) in peripheral tissues and decrease hepatic glucose production. TZDs are potent, synthetic ligands for peroxisome proliferator-activated receptor gamma (PPAR-γ), which mediates physiological responses by altering the transcription of genes that regulate glucose and lipid metabolism.
TZDs provide many benefits to patients with type 2 diabetes by improving glycaemic control and insulin sensitivity, thereby having the potential to decrease the risk of cardiovascular disease (CVD) associated with IR. TZDs are known to increase high density lipoprotein cholesterol (HDL-C) concentrations, low density lipoprotein (LDL) particle size, and LDL cholesterol (LDL-C) resistance to oxidation. In addition, TZDs decrease intima-media thickness and prevent re-stenosis after coronary stent implantations. These nonhypoglycaemic effects of TZD are thought to potentially decrease the risk of CVD. Some studies have reported the unwanted effects of rosiglitazone on the levels of total cholesterol (TC) and LDL-C concentrations and also on body weight. However, these studies are limited because of short-term patient follow-up. The long-term effects of TZDs are of particular interest because patients often use these drugs as a continuous therapy. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight in type 2 diabetic patients.
Summary and Introduction
Summary
Objective: Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight.
Design: Open labelled clinical study.
Patients and Measurements: We prospectively evaluated fasting serum glucose, haemoglobin A1c (HbA1c), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients.
Results: TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained.
Conclusions: HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.
Introduction
Thiazolidinediones (TZDs) are oral antihyperglycaemic agents that reduce insulin resistance (IR) in peripheral tissues and decrease hepatic glucose production. TZDs are potent, synthetic ligands for peroxisome proliferator-activated receptor gamma (PPAR-γ), which mediates physiological responses by altering the transcription of genes that regulate glucose and lipid metabolism.
TZDs provide many benefits to patients with type 2 diabetes by improving glycaemic control and insulin sensitivity, thereby having the potential to decrease the risk of cardiovascular disease (CVD) associated with IR. TZDs are known to increase high density lipoprotein cholesterol (HDL-C) concentrations, low density lipoprotein (LDL) particle size, and LDL cholesterol (LDL-C) resistance to oxidation. In addition, TZDs decrease intima-media thickness and prevent re-stenosis after coronary stent implantations. These nonhypoglycaemic effects of TZD are thought to potentially decrease the risk of CVD. Some studies have reported the unwanted effects of rosiglitazone on the levels of total cholesterol (TC) and LDL-C concentrations and also on body weight. However, these studies are limited because of short-term patient follow-up. The long-term effects of TZDs are of particular interest because patients often use these drugs as a continuous therapy. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight in type 2 diabetic patients.
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