Comparison of three treatment approaches to decreasing cardiovascular disease risk in nondiabetic insulin-resistant dyslipidemic subjects

The efficacy of fenofibrate (FEN), rosiglitazone (RSG), or a calorie-restricted diet (CRD) to reduce cardiovascular disease risk was compared in 37 overweight/obese, insulin resistant, nondiabetic individuals. Measurements were made of insulin sensitivity, fasting lipid and lipoprotein concentrations, and postprandial plasma glucose, insulin, free fatty acid, and triglyceride concentrations, before and after three months of treatment with FEN, RSG, or the CRD. Weight fell in the CRD group, but did not change significantly following treatment with either drug. Insulin sensitivity improved significantly in the CRD and RSG-treated groups, but to a greater extent in those given RSG, without a significant difference when comparing FEN treatment to the CRD. Total cholesterol concentrations were significantly lower following FEN and CRD. Fasting plasma triglyceride concentrations decreased significantly in FEN-treated and CRD groups, but postprandial concentrations decreased only in the FEN-treated subjects. Significant decreases in postprandial glucose and insulin concentrations were only seen in the RSG-treated and CRD groups. FEN administration improved the dyslipidemia in these subjects, without changing insulin sensitivity, whereas insulin sensitivity was enhanced in RSG-treated patients, without improvement in the dyslipidemia. Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia, but the change in the former was less than in RSG-treated individuals, and the improvement in lipid metabolism not as great as with administration of FEN. In conclusion, there does not appear to be one therapeutic intervention that effectively treats all the metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease.