¹Department of Endocrinology, Metabolism and Nutrition, University Hospital, Gasthuisberg, Leuven, Belgium

²University Hospital St Luc, Brussels, Belgium

³Département de Médecine, Centre Hospitalier Universitaire Sart Tilman, Liége, Belgium

⁴Department of Endocrinology, Metabolism and Clinical Nutrition, University Hospital Antwerp, Edegem-Antwerp, Belgium

Correspondence to: E Muls, Department of Endocrinology, Metabolism and Nutrition, Herestraat 49, B-3000 Leuven, Belgium. E-mail: Erik.Muls@uz.kuleuven.ac.be

^aObesity Linked with Hypercholesterolemia treated with Xenical.

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.

International Journal of Obesity (2001) 25, 1713-1721

obesity; orlistat; lipase inhibition; lipids; cardiovascular risk factors