In addition to reductions in body mass index and weight, the treated adolescents had improvements in disease risk factors associated with obesity. They had lower levels of triglycerides and higher levels of high-density lipoprotein cholesterol, which are related to heart disease, and lower levels of insulin, a risk factor for diabetes. The only significant side effect was tachycardia, or rapid heart beat.
Although sibutramine, sold under the brand name Meridia, is currently used in adults with obesity, "this is the first large multicenter trial of sibutramine for obese adolescents," said study leader Robert I. Berkowitz, M.D., chief of Child and Adolescent Psychiatry at The Children's Hospital of Philadelphia. "In fact, there have been few trials evaluating any obesity drugs in adolescents."
Behavior therapy alone, said Dr. Berkowitz, usually provides only modest weight loss in adolescents, and thus medication may provide an additional treatment option for this age group.
The study enrolled 498 severely obese adolescents, aged 12 to 16, in 33 outpatient clinics throughout the United States from 2000 to 2002. The patients were randomized into two double-blinded groups, one receiving sibutramine and one receiving a placebo, while both groups received behavior therapy.
Each treatment center had its own behavior therapy program, with flexible modification approaches that included self-monitoring of eating habits and physical activity, stress management, stimulus control, problem solving and social support. Counselors encouraged patients to increase their physical activity and reduce their sedentary behaviors, and provided nutritional counseling.
At the end of the study, the 281 adolescents in the treatment group lost an average of 14 pounds, while the 79 patients in the control group gained an average of four pounds. Body mass index (BMI) decreased by 9.4 percent in the treatment group compared to 1.2 percent in the control group. Patients in both groups gained height and matured sexually at the same rate.
The standard definition of overweight in adolescents usually refers to those with a BMI greater than the 95th percentile for age and sex. This study focused on heavier patients, those with a BMI two units more than the 95th percentile, placing them at roughly the 97th percentile. Their mean weight was approximately 215 pounds.
At the end of the study, 33 percent of the patients who received sibutramine, compared to 7.6 percent in the control group, no longer had a BMI that was 2 units above the 95th percentile. Furthermore, 16.7 percent of the treated patients had their BMI drop below the 95th percentile (vs. 3.8 percent in the control group).
"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," said Dr. Berkowitz. "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."
As with any medication, cautioned Dr. Berkowitz, patients considering the use of sibutramine would need to consult with their physicians. Patients who take sibutramine require regular monitoring of pulse and blood pressure, and interactions with other specific medications may indicate that sibutramine should not be prescribed. In addition, the U.S. Food and Drug Administration does not currently approve using sibutramine in adolescents under age 16.
Because this study covered only one year of treatment, added Dr. Berkowitz, further investigation should analyze long-term weight management and health outcomes for adolescents with obesity. Other studies should focus on possible long-term risks of medication versus risks of continued weight gain. He concluded, "Although much research remains to be done, our findings are encouraging for clinicians, and may offer treatment options for obese adolescents for whom behavioral therapies alone are not successful."
The study was funded by Knoll Pharmaceutical Company (now Abbott Laboratories), which manufactures sibutramine. Dr. Berkowitz's co-authors were Ken Fujioka, M.D., of Scripps Clinic, San Diego; Stephen R. Daniels, M.D., Ph.D., of Children's Hospital and Medical Center, Cincinnati; Alison G. Hoppin, M.D. of Massachusetts General Hospital Weight Center; Stanford Owen, M.D., of the Center for Health Management, Gulfport, Miss.; Arlette C. Perry, Ph.D., of the University of Miami; Melinda S. Sothern, Ph.D., Louisiana State University Health Sciences Center; and Cheryl L. Renz, M.D., Mark A. Pirner, M.D., Ph.D.; Julia K. Walch, B.S.; Olga Jasinsky, M.B.A.; Ann C. Hewkin, M.Sc.; and Vicky A. Blakesley, M.D., Ph.D., all of Abbott Laboratories.
The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit www.chop.edu.
Journal
Annals of Internal Medicine