Randomised 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 effica cy and tolerance of orlistat, a gastrointestinal lipase inhibitor, in promo ting weight loss and preventing weight regain in obese patients over a 2-ye ar period. Methods. 743 patients (body-mass index 28-47 kg/m(2)), recruited at 15 Euro pean centres, entered a 4-week, single-blind placebo lead-in period on a sl ightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (thre e times a day) or placebo for 1 year in conjunction with the hypocaloric di et. In a second 52-week double-blind period patients were reassigned orlist at or placebo with a weight maintenance (eucaloric) diet. Findings. From the start of lead-in to the end of year 1, the orlistat grou p lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] SI om randomisation to t he end of year 1). During year 2, patients who continued with orlistat rega ined, on aver age, half as much weight as those patients switched to placeb o (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the pla cebo group. Gastrointestinal adverse events were more common in the or orli stat group. Other adverse symptoms occurred at a similar frequency during b oth 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 respect to efficacy and adverse events.