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A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects.

AbstractBACKGROUND:
Treatment of obese subjects with topiramate has recently been associated with significant weight loss in a 6-month dose-ranging study.
OBJECTIVE:
To investigate the long-term efficacy and safety of topiramate in obese subjects.
DESIGN:
Randomised, double-blind, placebo-controlled study investigating three doses of topiramate: 96, 192, and 256 mg/day. All subjects also participated in a nonpharmacological weight-loss programme.
SUBJECTS:
The study included 1289 subjects 18-75 y with a body mass index >/=30 kg/m(2) and <50 kg/m(2) in the absence of comorbidities, or >/=27 kg/m(2) and <50 kg/m(2) in the presence of controlled hypertension and/or dyslipidaemia.
DURATION:
The original study design was for a 6-week, single-blind, placebo run-in phase followed by an 8-week titration phase and 2 y of maintenance at the assigned dose. Sponsor ended study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Therefore, none of the subjects completed the full 2 y of treatment. Efficacy results are based on subjects who were enrolled early enough to have had an opportunity to complete 1 y at their assigned dose (modified intent-to-treat population, MITT) before learning of the decision to terminate the study. Safety results are based on all subjects who took at least one dose of study medication.
RESULTS:
The safety population consisted of 1282 subjects, and the MITT efficacy population was 854 subjects. At 60 weeks, subjects in the placebo group lost 1.7% of their baseline body weight, while subjects in the topiramate 96, 192, and 256 mg/day treatment groups lost 7.0, 9.1, and 9.7%, respectively (P<0.001, MITT, last observation carried forward). Weight loss >/=5% of baseline weight was achieved by 18% of subjects in the placebo arm vs 54, 61, and 67% of subjects receiving topiramate 96, 192, and 256 mg/day, respectively; weight loss >/=10% was achieved by 6 vs 29, 40, and 44%, respectively (P<0.001). Weight loss was accompanied by significant improvements in blood pressure (systolic/diastolic changes of +0.4/+1.0, -3.1/-1.3, -5.7/-3.4, and -4.6/-2.4 mmHg were observed for placebo, topiramate 96 mg/day, 192 mg/day, and 256 mg/day, respectively, P<0.001) and glucose and insulin. The most common adverse events more frequently observed in topiramate-treated subjects occurred mostly during the titration phase and were related to the central or peripheral nervous system and included paresthesia, difficulty with concentration/attention, depression, difficulty with memory, language problems, nervousness, and psychomotor slowing.
CONCLUSION:
Topiramate treatment of obese subjects over the course of 1 y resulted in clinically significant weight loss. Improvements were also observed in blood pressure and glucose tolerance.
AuthorsJ Wilding, L Van Gaal, A Rissanen, F Vercruysse, M Fitchet, OBES-002 Study Group
JournalInternational journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity (Int J Obes Relat Metab Disord) Vol. 28 Issue 11 Pg. 1399-410 (Nov 2004) England
PMID15486569 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Obesity Agents
  • Blood Glucose
  • Topiramate
  • Fructose
Topics
  • Adult
  • Anti-Obesity Agents (administration & dosage, adverse effects, therapeutic use)
  • Blood Glucose (analysis)
  • Blood Pressure (drug effects)
  • Depression (chemically induced)
  • Diet, Reducing
  • Double-Blind Method
  • Drug Administration Schedule
  • Exercise Therapy
  • Female
  • Follow-Up Studies
  • Fructose (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
  • Glucose Tolerance Test
  • Humans
  • Male
  • Middle Aged
  • Obesity (diet therapy, drug therapy, psychology)
  • Paresthesia (chemically induced)
  • Suicide (psychology)
  • Topiramate

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