The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome

Background Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA2) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS). Objective The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA2 activity and LDL phenotype in overweight and obese patients (body mass index > 28 kg/m2) with MetS. Methods Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. Results Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p < 0.05) together with a greater increase in LDL particle diameter (p < 0.05) compared with group O. Total plasma Lp-PLA2 activity significantly decreased in all treatment groups. The reduction of Lp-PLA2 was more pronounced with OF administration compared with each monotherapy (p < 0.05). Conclusion Orlistat and fenofibrate exhibited favorable effects on Lp-PLA2 activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.