A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Topiramate Controlled Release in the Treatment of Obese Type 2 Diabetic Patients

  1. Julio Rosenstock, MD1,
  2. Priscilla Hollander, MD2,
  3. Kishore M. Gadde, MD3,
  4. Xiang Sun, PHD4,
  5. Richard Strauss, MD4,
  6. Albert Leung, MD, PHD4 and
  7. for the OBD-202 Study Group
  1. 1Dallas Diabetes and Endocrine Center, Dallas, Texas
  2. 2Baylor Hospital, Dallas, Texas
  3. 3Duke University School of Medicine, Durham, North Carolina
  4. 4Johnson & Johnson Pharmaceutical Research & Development, Raritan, New Jersey
  1. Address correspondence and reprint requests to Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center at Medical City, 7777 Forest Lane, C-685, Dallas, TX 75230. E-mail: juliorosenstock{at}dallasdiabetes.com

Abstract

OBJECTIVE—This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin.

RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes, BMI ≥27 kg/m2, A1C >6.5 and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.

RESULTS—A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P < 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P < 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related.

CONCLUSIONS—Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.

Footnotes

  • Published online ahead of print at http://care.diabetesjournals.org on 15 March 2007. DOI: 10.2337/dc06-2001. Clinical trial reg. no. NCT00231647, clinicaltrials.gov.

    This report describes an investigational use of topiramate. Topiramate is not approved in any country for the treatment of obesity or diabetes.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted March 6, 2007.
    • Received September 25, 2007.
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  1. Diabetes Care vol. 30 no. 6 1480-1486
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