Long-Term Follow-up of a Randomized, Placebo-Controlled Trial of Orlistat in African-American and Caucasian Adolescents with Obesity-Related Comorbid Conditions

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 660-676-Clinical Obesity Treatment
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-666
Tania Andrea Condarco*1, Roya Sherafat-Kazemzadeh1, Jennifer R. McDuffie1, Sheila Brady1, Christine Salaita2, Nancy G. Sebring2, Marian Tanofsky-Kraff1, Deborah Young-Hyman1, Lisa B. Yanoff1, Margaret Keil1, David M. Savastano1, Lauren B. Shomaker1, Diane C. Adler-Wailes1, James Reynolds3, Van S Hubbard4, Karim Anton Calis3 and Jack Adam Yanovski1
1NICHD/NIH, Bethesda, MD, 2National Institutes of Health, Bethesda, MD, 3CC-NIH, Bethesda, MD, 4DNRC/NIH
Background: Orlistat is the only FDA-approved medication for treatment of obesity in adolescents. Published trials have reported small but significant effects on body weight and BMI during 1 year of orlistat treatment. However, little is known about orlistat’s efficacy among adolescents who have obesity-related comorbid conditions or its long-term effects on body weight.

Methods: We conducted a single-center, randomized, double-blind, placebo-controlled trial in 200 severely obese African-American and Caucasian adolescents (mean BMI 41.7±0.6 kg/m2), with at least one obesity related co-morbidity (hypertension, dyslipidemia, sleep apnea, or impaired glucose homeostasis). Subjects were randomized to orlistat 120 mg TID (n=100), or placebo (n=100) plus behavioral therapy and a multivitamin for 6mo. All subjects were then offered open-label orlistat treatment for 6mo and were subsequently followed for two additional years off study drug. Changes in BMI in each phase for orlistat and placebo groups were compared using Hierarchical Linear Modeling.

Results: At baseline, adolescents did not differ by sex, age, race, or BMI (P>0.45). During the randomized phase, subjects in the orlistat group had a small but significantly greater decrease in BMI (-1.72±0.24 vs. -0.70±0.24 kg/m2, P=0.002) compared to placebo. During the open-label phase (n=175), both groups had significant increases in BMI (p<0.001), with no significant difference between those who continued to take orlistat and those who switched from placebo to orlistat (+1.17±0.06 vs. +0.77±0.05 kg/m2, P=0.09). During two years of off-drug follow-up, adolescents who were originally randomized to orlistat (who received orlistat for 1 year) had a significantly slower increase in their BMI compared to those who were randomized to placebo and then given orlistat for 6mo (+0.04±0.37 kg/m2 vs. +2.14±0.32 kg/m2, P=0.005).

Conclusion: During the 6mo randomized phase, when treatment was combined with behavioral therapy, orlistat treatment led to a small but significant improvement in BMI compared to placebo among obese adolescents with obesity-related comorbidities. However, orlistat without continued behavioral therapy did not further decrease BMI during months 6-12, although those originally randomized to orlistat had significantly slower weight gain after drug discontinuation. Orlistat was only minimally effective for amelioration of obesity in severely obese adolescents with obesity-related medical complications.

Disclosure: DMS: Employee, GlaxoSmithKline, Employee, GlaxoSmithKline. JAY: Principal Investigator, Roche Pharmaceuticals. Nothing to Disclose: TAC, RS, JRM, SB, CS, NGS, MT, DY, LBY, MK, LBS, DCA, JR, VSH, KAC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm