The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study
OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients.DESIGN: A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (−600 kcal/day; ≤30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase.SUBJECTS: Patients with body mass index (BMI) 27–40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1–6.7 mmol/l).MEASUREMENTS: Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments.RESULTS: Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was−6.8% in the orlistat group and −3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of ≥5% (64 vs 39%) or ≥10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (−11.9% vs −4.0%; P<0.001) and LDL-C (−17.6 vs −7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (≥1 event in 64 vs 38% of patients).CONCLUSION: Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia.