Abstract
Objective:
To investigate the efficacy and safety of topiramate in obese subjects with type 2 diabetes treated with metformin.
Design:
This was a multicenter, double-blind, placebo-controlled trial. All subjects received a non-pharmacological program of diet, exercise and behavioral modification throughout the study; the assigned diet was 600 kcal/day less than the subject's individually calculated energy expenditure. After a 6-week single-blind placebo run-in, subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Following an 8-week titration period, subjects remained on their assigned dose for 52 weeks. However, the sponsor ended the study early in order to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. A total of 646 obese men and women (age: 18–75 years, body mass index: 27–50 kg/m2) with an established history of type 2 diabetes mellitus controlled by metformin monotherapy were randomized. Efficacy was assessed in a pre-determined modified intent-to-treat (MITT) population of 307 subjects whose randomization date would have allowed them to complete 24 weeks on study medication before the announcement of study termination.
Measurements:
Joint primary efficacy parameters were mean percent change in weight and change in glycosylated hemoglobin (HbA1c) from baseline to week 24.
Results:
Subjects in the placebo, topiramate 96 mg/day and topiramate 192 mg/day groups lost 1.7%, 4.5% (P<0.001) and 6.5% (P<0.001), respectively, of their baseline body weight and had absolute decreases in HbA1c of 0.1%, 0.4% (P<0.001) and 0.6% (P<0.001) (MITT, last observation carried forward). Topiramate-treated subjects also experienced statistically significant decreases in systolic blood pressure. Most common adverse events were paresthesia and events related to the central nervous system.
Conclusions:
Topiramate was effective for weight reduction and improvement in glycemic control in obese subjects with type 2 diabetes treated with metformin monotherapy. Further study in obese diabetics is warranted.
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Acknowledgements
This study was supported by Johnson & Johnson Pharmaceutical Research and Development. The members of the OBDM-002 Study Group are: Austria: R. Lober, Wr. Neustadt; H. Toplak, Graz; Canada: R. Aronson, Oakville, Ontario; C.K. Bowering, Edmonton, Alberta; H. Conter, Halifax, Nova Scotia; J. Janzen, Pointe Claire, Quebec; B. Lasko, Toronto, Ontario; L. Leiter, Toronto, Ontario; P. Whitsitt, Oshawa, Ontario; V. Woo, Winnipeg, Manitoba; P. Ziter, Windsor, Ontario; France: J.-D. Lalau, Amiens; M. Laville, Lyon; J.-L. Richard, Le Grau du Roi; Germany: H.-G. Dammann, Hamburg; H. Ditschuneit, Ulm; P. Grafinger, Linz; A. Hamann, Heidelberg; M. Hanefeld, Dresden; A. Luger, Wien; B. Paulweber, Salzburg; R. Prager, Wien; F. Winkler, Ebreichsdorf; Ireland: B. Buckley, Cork; B. Kinsley, Dublin; J. Nolan, Dublin; G. Sullivan, Co. Tipperary; Poland: E. Bandurska-Stankiewicz, Olsztyn; M. Gorska, Bialystok; P. Oledzki, Warszawa; E. Semetkowska-Jurkiewicz, Gdansk; M. Wojciechowska, Plock; D. Zytkiewicz-Jaruga, Wroclaw; South Africa: R. Moore, Natal; Spain: E. Esmatjes, Barcelona; X. Formiguera, Barcelona; R.G. Robles, Madrid; M. Serrano Rios, Madrid; Sweden: P-O Andersson, Eksjö; E. Eizyk, ängelholm; L. Groop, Malmö; T. Lindström, Linköping; A. Norrby, Göteborg; U. Rosenqvist, Motala; K. Wahlin, Värnamo; United Kingdom: C. Dayan, Weston-Super-Mare; K. Earle, London; N. Finer, Luton; C. Fox, Northampton; J. Fraser, Wigan; C. Harding, Cardiff; J. James, Manchester; P. Kopelman, London; S. Kumar, Birmingham; G. Leese, Dundee; J. Maroni, Glasgow; E. Masson, Hull; M. Press, London; G. Rayman, Ipswich; J. Robinson, North Liverpool; M. Salman, Birmingham; S. Sharma, Liverpool; H. Shaw, Berks; S. Taylor, Lancs; J.K. Wales, Leeds; J. Wilding, Liverpool.
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Toplak, H., Hamann, A., Moore, R. et al. Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Int J Obes 31, 138–146 (2007). https://doi.org/10.1038/sj.ijo.0803382
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DOI: https://doi.org/10.1038/sj.ijo.0803382
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