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.


METHODS
A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (-600 kcal/day; < or =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.


METHODS
Patients with body mass index (BMI) 27-40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1-6.7 mmol/l).


METHODS
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 > or =5% (64 vs 39%) or > 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 (> or =1 event in 64 vs 38% of patients).


CONCLUSIONS
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.
Muls
E
E
Department of Endocrinology, Metabolism and Nutrition, University Hospital, Gasthuisberg, Leuven, Belgium. Erik.Muls@uz.kuleuven.ac.be
Kolanowski
J
J
Scheen
A
A
Van Gaal
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001530:Belgium; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004038:Diet, Reducing; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000178:diet therapy / Q000188:drug therapy*; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000178:diet therapy / Q000188:drug therapy*; D000077403:Orlistat; D016896:Treatment Outcome; D015431:Weight Loss
D019440:Anti-Obesity Agents; D008078:Cholesterol, LDL; D007783:Lactones; D000077403:Orlistat; D002784:Cholesterol; D008049:Lipase