Abstract
BACKGROUND: 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/m2 and <50 kg/m2 in the absence of comorbidities, or ≥27 kg/m2 and <50 kg/m2 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.
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Acknowledgements
This trial was supported by Johnson & Johnson Pharmaceutical Research and Development, LLC. The members of the OBES-002 Study Group are: Dammann, Hanns-Gerd, Hamburg, Germany; Ditschuneit, Herwig H, Ulm, Germany; Eichler, Hans Georg, Vienna, Austria; Elte, Jan Willem, Rotterdam, The Netherlands; Finer, Nicholas, Luton, UK; Foerster, Hanns-Michael, Duisburg Baerl, Germany; Hamann, Andreas, Heidelberg, Germany; Hanefeld, Markolf, Dresden, Germany; Häring, Hans-Ulrich, Tübingen, Germany; Hoppichler, Friedrich, Salzburg, Austria; Klör, Hans-Ulrich, Giessen, Germany; Kopelman, Peter, London, UK; Laederach-Hofmann, Kurt, Bern, Switzerland; Lean, Michael, Glasgow, UK; Mathus-Vliegen, Elisabeth, Amsterdam, The Netherlands; Moore, Ray, Kwa-Zulu Natal, South Africa; Mustajoki, Pertti, Helsinki, Finland; Niskanen, Leo, Kuopio, Finland; Prager, Rudolf, Vienna, Austria; Rissanen, Aila, Helsinki, Finland; Rössner, Stephan, Huddinge, Sweden; Scheen, André, Sart Tilman, Liège, Belgium; Scheen, André, Quai Godefroid Kurth, Liège, Belgium; Sharma, Ayra Mitra, Berlin, Germany; Sjöström, Lars, Göteborg, Sweden; Usadel, Klaus-Henning, Frankfurt, Germany; Van der Merwe, Maria Teresa, Johannesburg, South Africa; Van Gaal, Luc, Edegem, Belgium; Wilding, John, Liverpool, UK; Zietz, Bettina, Regensburg, Germany.
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Wilding, J., Gaal, L., Rissanen, A. et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes 28, 1399–1410 (2004). https://doi.org/10.1038/sj.ijo.0802783
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DOI: https://doi.org/10.1038/sj.ijo.0802783
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