Effects of Sibutramine Treatment in Obese Adolescents

A Randomized Trial

  1. Robert I. Berkowitz, MD;
  2. Ken Fujioka, MD;
  3. Stephen R. Daniels, MD, PhD;
  4. Alison G. Hoppin, MD;
  5. Stanford Owen, MD;
  6. Arlette C. Perry, PhD;
  7. Melinda S. Sothern, PhD;
  8. Cheryl L. Renz, MD;
  9. Mark A. Pirner, MD, PhD;
  10. Julia K. Walch, BS;
  11. Olga Jasinsky, MBA;
  12. Ann C. Hewkin, MSc;
  13. Vicky A. Blakesley, MD, PhD; and
  14. for the Sibutramine Adolescent Study Group*
  1. From The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Scripps Clinic, San Diego, California; University of Cincinnati College of Medicine and Children's Hospital Medical Center, Cincinnati, Ohio; Massachusetts General Hospital, Boston, Massachusetts; Center for Health Management, Gulfport, Mississippi; University of Miami School of Education, Coral Gables, Florida; Louisiana State University Health Sciences Center and Pennington Research Center, New Orleans, Louisiana; and Abbott Laboratories, Abbott Park, Illinois.

    Abstract

    Background: Increased prevalence of adolescent obesity requires effective treatment options beyond behavior therapy.

    Objective: To see whether sibutramine reduced weight more than placebo in obese adolescents who were receiving a behavior therapy program.

    Design: 12-month, 3:1 randomized, double-blind trial conducted from July 2000 to February 2002.

    Setting: 33 U.S. outpatient clinics.

    Participants: 498 participants 12 to 16 years of age with a body mass index (BMI) that was at least 2 units more than the U.S. weighted mean of the 95th percentile based on age and sex, to the upper limit of 44 kg/m2.

    Interventions: Site-specific behavior therapy plus 10 mg of sibutramine or placebo. Blinded study medication dose was uptitrated to 15 mg or placebo at month 6 if initial BMI was not reduced by 10%.

    Measurements: Body mass index, waist circumference, body weight, fasting lipid and glycemic variables, safety, and tolerability.

    Results: Seventy-six percent of patients in the sibutramine group and 62% of patients in the placebo group completed the study. The estimated mean treatment group difference at month 12 (linear mixed-effects model) favored sibutramine for change from baseline in BMI (−2.9 kg/m2 [95% CI, −3.5 to −2.2 kg/m2]) and body weight (−8.4 kg [CI, −9.7 to −7.2 kg]) (P < 0.001 for both). The sibutramine group had greater improvements in triglyceride levels, high-density lipoprotein cholesterol levels, insulin levels, and insulin sensitivity (P ≤ 0.001 for all). The rate of tachycardia was greater with sibutramine vs. placebo (12.5% vs. 6.2%; difference, 6.3 percentage points [CI, 1.0 to 11.7 percentage points]) but did not lead to increased withdrawal (2.4% vs. 1.5%; difference, 0.9 percentage point [CI, −1.7 to 3.5 percentage points]).

    Limitations: The 1-year study duration precluded assessment of long-term weight maintenance and putative health benefits and harms, and 24% and 38% of the sibutramine and placebo groups, respectively, did not complete follow-up.

    Conclusions: Sibutramine added to a behavior therapy program reduced BMI and body weight more than placebo and improved the profile of several metabolic risk factors in obese adolescents.

    *For members of the Sibutramine Adolescent Study Group, see the Appendix.

    Article and Author Information

    • ClinicalTrials.gov identifier: NCT00261911.

    • Acknowledgments: The authors thank all the study investigators, as well as Knoll Pharmaceutical Company (now Abbott) for providing study drugs and sponsorship and Aimée Loar for support with statistical analysis.

    • Grant Support: By Knoll Pharmaceuticals (BASF Pharma), now Abbott.

    • Potential Financial Conflicts of Interest: Employment: C.L. Renz (Abbott), M.A. Pirner (Abbott), J.K. Walch (Abbott), O. Jasinsky (Abbott), A.C. Hewkin (Abbott), V.A. Blakesley (Abbott); Consultancies: R.I. Berkowitz (Abbott, Johnson & Johnson, Roche Laboratories, Sanofi-Aventis, Shionogi USA), K. Fujioka (Abbott), S.R. Daniels (Abbott); Honoraria: R.I. Berkowitz (Abbott, Roche Laboratories), K. Fujioka (Abbott); Stock ownership or options (other than mutual funds): C.L. Renz (Abbott), J.K. Walch (Abbott), O. Jasinsky (Abbott), A.C. Hewkin (Abbott); Grants received: R.I. Berkowitz (Abbott, Knoll Pharmaceuticals), K. Fujioka (Abbott), S.R. Daniels (Abbott), A.G. Hoppin (Abbott), V.A. Blakesley (Abbott); Patents pending: C.L. Renz (Abbott).

    • Requests for Single Reprints: Robert I. Berkowitz, MD, The Behavioral Health Center at The Children's Hospital of Philadelphia, 3440 Market Street, Suite 410, Philadelphia, PA 19104; e-mail, berkowitz{at}email.chop.edu.

    • Current Author Addresses: Dr. Berkowitz: The Behavioral Health Center at The Children's Hospital of Philadelphia, 3440 Market Street, Suite 410, Philadelphia, PA 19104.

    • Dr. Fujioka: Scripps Clinic, Suite 317, 12395 El Camino Real, San Diego, CA 92130.

    • Dr. Daniels: Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229.

    • Dr. Hoppin: Massachusetts General Hospital Weight Center, 50 Staniford Street, Boston, MA 02114.

    • Dr. Owen: Center for Health Management, 3300 15th Street, Gulfport, MS 39501.

    • Dr. Perry: University of Miami, 5202 University Drive, Coral Gables, FL 33124.

    • Dr. Sothern: Louisiana State University Health Sciences Center, 1600 Canal Street, Suite 800, New Orleans, LA 70112.

    • Dr. Renz and Ms. Hewkin: Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064.

    • Drs. Pirner and Blakesley, Ms. Walch, and Ms. Jasinsky: Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064.

    • Author Contributions: Conception and design: R.I. Berkowitz, K. Fujioka, M.S. Sothern, C.L. Renz, V.A. Blakesley.

    • Analysis and interpretation of the data: R.I. Berkowitz, K. Fujioka, S.R. Daniels, C.L. Renz, M.A. Pirner, J.K. Walch, O. Jasinsky, A.C. Hewkin, V.A. Blakesley.

    • Drafting of the article: R.I. Berkowitz, K. Fujioka, S.R. Daniels, M.A. Pirner, J.K. Walch, O. Jasinsky, A.C. Hewkin.

    • Critical revision of the article for important intellectual content: R.I. Berkowitz, K. Fujioka, S.R. Daniels, A.G. Hoppin, S. Owen, M.S. Sothern, C.L. Renz, M.A. Pirner, V.A. Blakesley.

    • Final approval of the article: R.I. Berkowitz, K. Fujioka, S.R. Daniels, S. Owen, A.C. Perry, M.S. Sothern, C.L. Renz, M.A. Pirner, A.C. Hewkin, V.A. Blakesley.

    • Provision of study materials or patients: R.I. Berkowitz, A.G. Hoppin, S. Owen, A.C. Perry, M.S. Sothern, V.A. Blakesley.

    • Statistical expertise: A.C. Hewkin.

    • Obtaining of funding: R.I. Berkowitz, M.S. Sothern, V.A. Blakesley.

    • Administrative, technical, or logistic support: K. Fujioka, S.R. Daniels, A.C. Perry, M.S. Sothern, O. Jasinsky.

    • Collection and assembly of data: K. Fujioka, S.R. Daniels, A.C. Perry, M.S. Sothern, M.A. Pirner.

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