The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia

ABSTRACT

Background: Increased concentrations of low density lipoprotein cholesterol (LDL-C), as well as of small dense LDL-C (sdLDL-C), are considered as cardiovascular risk factors.

Objective: An assessment of the effects of ezetimibe and orlistat administration, alone or in combination, on LDL-C and sdLDL-C levels (primary endpoint), as well as on anthropometric variables and metabolic parameters (secondary endpoints) in overweight and obese patients [body mass index (BMI) > 28 kg/m²] with hypercholesterolaemia [total cholesterol > 200 mg/dL (5.2 mmol/L)].

Methods: Eighty six subjects were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg, 3 times daily (O group), ezetimibe 10 mg/day (E group) or both (OE group) for 6 months.

Results: Significant reductions in LDL-C (−19%, −21%, −32% in groups O, E and OE, respectively, all p < 0.01 vs. baseline) and sdLDL-C levels (−45%, −48%, −76% in groups O, E, OE, respectively, all p < 0.01 vs. baseline) were observed. Group OE experienced a significantly greater reduction in LDL-C and sdLDL-C levels compared with groups O and E (p < 0.05). Furthermore, significant reductions of BMI, homeostasis model assessment (HOMA) index, serum uric acid, transaminase activities and plasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity were observed in the O and OE groups. Gamma-glutamyl transpeptidase activity and Lp-PLA₂ activity improved significantly more with the combination treatment compared with either orlistat or ezetimibe monotherapy.

Conclusions: Orlistat and ezetimibe combination had a more favourable effect on LDL-C and sdLDL-C levels in overweight and obese hypercholesterolaemic patients than either drug alone. Furthermore, orlistat, alone or in combination with ezetimibe, additionally improved several anthropometric and metabolic variables.

Key words: :

• Body weight
• Ezetimibe
• Low density lipoprotein cholesterol (LDL-C)
• Obesity
• Orlistat
• Phospholipase A₂
• Small dense LDL
• Triglycerides

Acknowledgement

Declaration of interest: This study was conducted independently; no company or institution supported it financially. Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies.