RANDOMIZED PLACEBO-CONTROLLED TRIAL OF ORLISTAT FOR WEIGHT-LOSS AND PREVENTION OF WEIGHT REGAIN IN OBESE PATIENTS

Background We undertook a randomised controlled trial to assess the ef ficacy and tolerability of orlistat, a gastrointestinal lipase inhibit or, in promoting weight loss and preventing weight regain in obese pat ients over a 2-year period. Methods 743 patients (body-mass index 28-4 7 kg/m(2)), recruited at 15 European centres, entered a 4-week, single -blind, placebo lead-in period on a slightly hypocaloric diet (600 kca l/day deficit). 688 patients who completed the lead-in were assigned d ouble-blind treatment with orlistat 120 mg (three times a day) or plac ebo for 1 year in conjunction with the hypocaloric diet. In a second 5 2-week double-blind period patients were reassigned orlistat or placeb o with a weight maintenance (eucaloric) diet. Findings From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 k g]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of y ear 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an addition al 0.9 hg during year 2, compared with a mean regain of 2.5 kg in pati ents who continued on placebo (p<0 001). Total cholesterol, low-densit y lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, a nd concentrations of glucose and insulin decreased more in the orlista t group than in the placebo group. Gastrointestinal adverse events wer e more common in the orlistat group. Other adverse symptoms occurred a t a similar frequency during both treatments. Interpretation Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with resp ect to efficacy and adverse events.