The role of orlistat in the treatment of obese patients with mild to moderate hypercholesterolaemia: consequences for coronary risk

This study investigated the effect of orlistat on weight loss and serum lipid parameters in obese patients with hypercholesterolaemia. A total of 215 adult obese patients (body mass index ≥30 kg/m2) with hypercholesterolaemia (total plasma cholesterol ≥6.5 mmol/L or plasma low density lipoprotein cholesterol ≥4.2 mmol/L) were recruited for screening at 12 out-patient clinics in the UK. Of these, 142 patients were randomised to receive double-blind treatment for 24 weeks with orlistat 120 mg (n=71) or placebo (n=71) three times daily in combination with a mildly hypocaloric diet. Patients completing the double-blind phase (orlistat n=42, placebo n=55) were eligible to enter a further 28-week open-label phase and received orlistat 120 mg three times daily in combination with the hypocaloric diet.
Mean weight loss after 24 weeks was 4.4 kg (4.4%) in the orlistat group vs. 2.6 kg (2.5%) with placebo (p<0.01). At the end of the double-blind phase, 44.0% of orlistat-treated patients vs. 18.0% of placebo recipients had lost ≥5% of their initial body weight (p<0.001), and 7.6% vs. 4.2% had lost ≥10% (p=NS). Patients who continued on orlistat during the open-label phase had a mean weight loss of 4.97 kg (4.86%) after 52 weeks. Patients who switched to orlistat had a mean weight loss of 4.28 kg (4.23%). Orlistat was associated with significantly greater reductions than placebo in plasma total cholesterol (-10.88 + 1.36% vs. -3.25 + 1.33%; p<0.001) and LDL-cholesterol (-14.14 + 2.68% vs. -3.68 + 3.61%; p<0.05) during the double-blind phase. Despite similar weight loss at the end of the 52-week period, patients who remained on orlistat throughout the study had greater improvements in plasma lipid concentrations than patients who switched to orlistat after 24 weeks.
Orlistat, in combination with a mildly hypocaloric diet, promotes clinically meaningful weight loss and improvements in lipid concentrations in obese patients with hypercholesterolaemia.