PHOENIX — Orlistat produced modest weight loss in extremely obese adolescents but failed to reverse comorbidities associated with metabolic syndrome in a randomized, placebo-controlled trial conducted by the National Institutes of Health.
Teenagers treated with orlistat (Xenical) lost more weight than did those on placebo after 6 months of treatment, but measures of blood pressure, cholesterol, insulin resistance, and fat-soluble vitamins were not significantly different—except for triglycerides, which were lower in the placebo group (P = .05).
“Orlistat really cannot be routinely recommended for treatment of obese-adolescents for comorbid conditions associated with obesity,” Dr. Jack A. Yanovski, the principal investigator, concluded during his presentation of the data at the annual scientific meeting of the Obesity Society.
Dr. Yanovski, head of the unit on growth and obesity within the National Institute of Child Health and Human Development, noted that orlistat gained approval for use in obese 12- to 16-year-olds in 2003 after a large randomized trial sponsored by Hoffmann-La Roche Inc. showed a modest but statistically significant reduction in body mass index (BMI) for this population. Only a quarter of participants met metabolic syndrome criteria, however, and changes in lipids, glucose, blood pressure, and insulin resistance were not significant.
Roche contributed orlistat and placebo for the current study, which enrolled 200 overweight black and white teenagers, all of whom had at least one comorbidity associated with metabolic syndrome. The group was evenly randomized: 100 participants to the full adult dose of 120 mg of orlistat three times per day and 100 teens to placebo. All were given a low-calorie diet.
The population was about 65% female and 61% black with an average age of about 14.6 years and average BMI of 41.7 kg/m
The orlistat group lost significantly more weight: −2.9 kg. vs. −0.6 kg for the placebo group. The orlistat group also had a significantly greater reduction in BMI (−1.72 vs. −0.70) and in fat mass (−3.9 kg. vs. −1.4 kg).
Blacks lost significantly less weight on orlistat than did whites, but orlistat was just as efficacious when weight gain in the black placebo group was taken into account. For blacks, the difference between weight loss on orlistat and weight gain on placebo was 2.5 kg. Whites lost whether they were on orlistat or placebo, but they lost more on orlistat with a similar difference of 2.2 kg.
Liver enzymes were significantly and unexpectedly higher with orlistat, he reported. Gastrointestinal side effects also were more common, but described as short in duration and well tolerated.
Although the trial was blinded, Dr. Yanovski reported most participants in the orlistat arm guessed correctly that they were on the study medication—possibly as a result of the GI side effects associated with orlistat.