PHILADELPHIA -- Extremely overweight teens lost an average of 14 pounds in one year with a combination of behavioral therapy and the weight-loss drug Meridia (sibutramine), researchers reported.
PHILADELPHIA, July 18 -- Extremely obese teens lost an average of 14 pounds in one year with a combination of behavioral therapy and the weight-loss drug Meridia (sibutramine), researchers reported.
In contrast, teens on a combination of behavioral therapy and placebo gained an average of four pounds in 12 months, reported Robert I. Berkowitz, M.D., chief of child and adolescent psychiatry at Children's Hospital of Philadelphia, and colleagues in 32 other centers, in the July 18 issue of the Annals of Internal Medicine.
In addition to weight loss and body mass index reductions, obese adolescents who received the active drug and behavioral therapy had improvements in lipid profiles and lower insulin levels and improved insulin sensitivity, the authors reported.
Participants in the active drug group had twice the rate of tachycardia as those in the placebo group, although this side effect did not require withdrawal from the trial, the authors noted.
"At the end of a year of treatment, one-third of the adolescents who received medication were no longer severely overweight, and one out of six who were treated dropped below the standard definition of being overweight," Dr. Berkowitz said. "We know that moderate weight loss in adults helps prevent or delay progression to type 2 diabetes. This may also be true in adolescents, although this study cannot address that question."
Dr. Berkowitz and colleagues at 33 outpatient clinics in the United States conducted a one-year randomized, double blind trial comparing Meridia plus behavioral therapy with placebo plus behavioral therapy in 498 adolescents from the ages of 12 to 16.
The participants all had BMIs that were at least two units higher than the U.S. weighted mean of the 95th percentile based on age and sex, with an upper limit of a BMI of 44 kg/m2.
The teens were randomized on a 3:1 basis to behavioral therapy plus 10 mg Meridia daily, or therapy plus placebo. The medication dose was titrated upwards to 15 mg daily (or placebo) if at six months there was not a reduction of at least 10% in BMI over baseline.
Behavioral therapy interventions, which were left up to the individual treatment sites, included self-monitoring of eating habits and physical activity, stress management, stimulus control, problem solving, and social support. Patients also received exercise and nutrition counseling.
The primary study outcomes were BMI, waist circumference, body weight, fasting lipid and glycemic variables, safety, and tolerability.
In all, 281 patients (76%) who received Meridia and 79 (62%) of those who received placebo completed the study.
Using a linear mixed-effects model, the investigators determined that patients in the Meridia group had a significantly greater estimated mean change from baseline in BMI, at -2.9 kg/m2 (95% confidence interval, -3.5 to -2.2 kg/m2, P <0.001) and in body weight at -8.4 kg/-18.5 lbs (95% CI, -9.7 to -7.2 kg. P< 0.001).
Participants in the Meridia group lost an average of 6.4 kg (14 lbs), compared with an average weight gain of 1.8 kg (4 lbs) in the placebo group
BMI decreased by a mean 9.4% in the treatment group compared with 1.2% among controls. Rates of sexual maturation and growth were similar in the two groups.
At the end of the study, 33%f the patients who received Meridia no longer had a BMI that was two units above the 95th percentile, compared with 7.6% of controls.
In addition, 16.7% of those on the active drug had a decline in BMI to below the 95th percentile, compared with 3.8% of those on placebo.
The participants who received Meridia also had greater improvements in triglyceride levels, HDL levels, insulin levels, and insulin sensitivity (P< 0.001 for all).
The only significant adverse effect was tachycardia, which occurred in 12.5% of those on Meridia, compared with. 6.2% of those on placebo, but this difference did not lead to a significant difference in withdrawals, the authors noted. Constipation, dry mouth, dizziness, and insomnia were more frequent in the Meridia group, consistent with the mechanism of action of the drug but these differences did not reach statistical significance.
They acknowledged that the study was limited by its relatively brief (one-year) duration, which did not allow for assessment of weight maintenance or health benefits of the weight loss.
In an accompanying editorial, William H. Dietz, M.D., Ph.D., of the division of nutrition and physical activity at the CDC in Atlanta, noted that the investigators did not evaluate the effect of the behavioral interventions separately from that of Meridia, making it difficult to know what percentage of weight and BMI loss could be attributed to increased physical activity.
"Implementing weight-control strategies requires efforts across several settings," Dr. Dietz wrote. "Parents should limit access to calorically dense foods and control television-watching time. Clinicians should promote breastfeeding, reduced soft drink intake, reduced television time, and increased physical activity. Schools can restore physical education and provide nutritionally sound choices. Communities should increase access to recreational facilities. "
"These multisectoral and multicomponent strategies to prevent weight gain in children and adolescents may also help to sustain the weight losses that Berkowitz and colleagues worked so hard to achieve in obese adolescents," he added.
The study was funded by Abbott, maker of Meridia.