Objective: To assess the efficacy and tolerability of orlistat (Xenical) in producing and maintaining weight loss over a 12-month period.
Design: Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.
Setting: Five centres in the UK.
Subjects: 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74-144 kg).
Interventions: All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.
Main outcome measures: Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and beta carotene.
Results: Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P < 0.05), and 28% and 17%, respectively (P = 0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P < 0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein: high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and beta carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P < 0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.
Conclusions: Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (> or = 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.