What is the long-term efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity in primary care?

BACKGROUND: National Institutes of Health guidelines for the treatment of obesity recommend a 10% weight loss from initial bodyweight. Pharma-co therapy may help achieve this goal. However, some agents have been associated with serious side effects and inadequate long-term effectiveness.

POPULATION STUDIED: The authors recruited 796 obese men and women with a body mass index (BMI) of 30 to 44 kg per m² from 17 primary care practices. They excluded patients who had any clinically significant chronic conditions; had recently changed smoking status; were taking drugs known to affect body weight; or with substance abuse, eating disorders, or reported weight loss of 4 kg or more. The study population was 90% white and 78% women.

STUDY DESIGN AND VALIDITY: This was a randomized double-blind placebo-controlled multicenter trial. Eligible subjects were prescribed a reduced energy diet (1200-1500 kcal/day) at the beginning of a 4-week single-blind placebo run-in period. The 635 patients who were at least 75% compliant by placebo pill count were randomized to receive placebo, orlistat 60 mg 3 times daily, or orlistat 120 mg 3 times daily for 1 year. Allocation was adequately concealed (personal communication) and intention-to-treat analysis was reported. Calories were increased by 300 per day for those patients who continued to lose weight at the end of the first year, and therapy was continued for another year. Patients watched behavior modification videos and received written weight management materials. Patients were asked to increase physical activity, but compliance was not monitored. Physicians assessed body weight, vital signs, and adverse events 10 times during the trial. At the end of 2 years, 57% of the placebo group and 46% of patients in each of the orlistat groups had withdrawn from the study.

OUTCOMES MEASURED: Change in body weight was the primary end point. Secondary end points were blood pressure, adverse drug effects, and serum lipid, glucose, and insulin levels.

RESULTS: At the end of 1 year more patients in the orlistat group lost at least 5% of their initial body weight than patients taking the placebo (50.5% vs 30.7%, P <.001; number needed to treat [NNT]=5.1). At the end of 2 years, this trend continued (34.3% vs 24.1%, P=.02; NNT=9.8). At the end of 1 year, more patients in the orlistat group lost 10% or more of their initial body weight than the patients taking the placebo (28.6% vs 11.3%, P <.001; NNT=5.8). The trend continued at 2 years (18.6% vs 6.6%, P=.001; NNT=8.3). Body weight lost was 1.65±0.62 kg in the placebo group and 5.02±0.73 kg in the orlistat group at the end of 2 years.