Question

• In obese adolescents, does pharmacotherapy combined with diet and exercise versus diet and exercise alone decrease BMI and improve weight loss?

Clinical Bottom Lines

1. Orlistat, in combination with diet, exercise, and behavior modification improves weight management in obese adolescents.
2. No major safety issues were identified after one year.
3. Further follow up studies for sustained weight management and safety are needed

Summary of Key Evidence

1. A randomized double-blind controlled trial in which following a 2-week single blind placebo lead in period, 539 participants entered a 54 week multicenter treatment period in which they were randomized at a 2:1 ratio to receive 120 mg of Orlistat or placebo tid in addition to a hypocaloric diet, exercise, and behavior therapy.¹
2. Inclusion criteria were adolescents 12-16 years of age with a BMI of 2 units or higher than the US weighted mean for the 95th percentile based on age and sex.
3. Exclusion criteria were participants with any of the following: BMI of 44 or higher; body weight of 130 kg or higher or less than 55 kg; weight loss of 3 kg or more within 3 months prior to screening; diabetes requiring medication; obesity associated with genetic disorders; history or presence of psychiatric disease; use of dexamphetamine or methylphenidate; active gastrointestinal tract disorders; ongoing bulimia or laxative abuse; or the use of anorectics or weight-reduction treatments during the 3 months before randomization.
4. There was a decrease in BMI in both treatment groups up to week 12. However, after the 12-week period, BMI remained stable with the Orlistat group but increased beyond baseline with the placebo group. At the end of the study, BMI had decreased by 0.55 from baseline with Orlistat, but increased by 0.31 with placebo (p=.001).
5. 26.5% of adolescents treated with Orlistat achieved a 5% or more reduction in BMI vs. 15.7% in the placebo group (p=.005, NNT=9) and 13.3% vs. 4.5% achieved a 10% or more decrease (p=.002, NNT=11).
6. At the end of the study, weight had increased 3.14 kg with placebo and 0.53 kg with Orlistat treated participants (p<0.001).
7. No significant differences were found between the 2 groups with respect to changes in lipid, glucose or insulin level. Participants treated with Orlistat experienced significantly greater decreases from baseline in both waist circumference (p=0.01) and hip circumference (p=0.01) along with diastolic blood pressure (p=0.04) than participants receiving placebo.
8. 12 Orlistat participants (3.4%) and 3 placebo participants (1.6%) discontinued treatment due to adverse side effects.
9. No major safety issues were reported.
10. The most common adverse events were GI-related and were more common in the Orlistat treated participants.

Additional Comments

• Diet, exercise, and behavioral modification were not standardized among treatment centers.
• Using the last observations carried forward method assumes that the individual data at the time of drop-out is representative of the data at the end of the study if the participant had completed it. In most cases, when treatment improves the condition over time, this method is a conservative bias in which the drop-out value is not as good as if the person had completed the study. However in this study, the effect of Orlistat is more substantial in the beginning but weakens as time goes on; by using the last observation carried forward method, it might have led to a better outcome especially if the drop out rate was during the beginning of the study.
• Although the results were statistically significant, one may argue that the treatment effects from Orlistat were modest (decrease of 2.61 kg in weight and 0.86 in BMI from the placebo participants over 1 year) and may not be substantial enough to sustain treatment in adolescents. On the other hand, slowing weight gain can have benefits such as delaying the development of obesity-related complications such as type 2 diabetes.
• Patient population was highly selective which may affect the generalizability of these results.
• Study duration was one year and longer follow-up studies are needed to allow assessment of efficacy and safety beyond one year.

Citation

1. Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of Orlistat on weight and body composition in obese adolescents: A randomized controlled trial. JAMA 2005; 293:2873-83.

CAT Author: Ami Shah, MD

CAT Appraisers: James Gurney, PhD

Date appraised: May 24, 2006