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
JULIO ROSENSTOCK, MD1
PRISCILLA HOLLANDER, MD2
KISHORE M. GADDE, MD3
XIANG SUN, PHD4
RICHARD STRAUSS, MD4
ALBERT LEUNG, MD, PHD4
FOR THE OBD-202 STUDY GROUP
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
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
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 im-
proved 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 albu-
min excretion. Adverse events were predominantly neuropsychiatric or central and periph-
eral nervous system related.
CONCLUSIONS — Topiramate CR treatment produced significant weight loss and mean-
ingful 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.
Diabetes Care 30:1480–1486, 2007
type 2 diabetes is considered overweight
icantly improve multiple parameters of
metabolic control (4).
ders and the prophylaxis of migraine head-
aches (5). Weight loss was incidentally but
in these neurologic indications, despite no
specific dietary interventions. Recently re-
ported placebo-controlled trials performed
in nondiabetic and diabetic populations
11). The controlled-release (CR) formula-
tion of topiramate that utilizes an osmotic
pump technology was developed to deliver
once-daily dosing with improved tolerabil-
This study aimed to evaluate the effi-
cacy and safety of topiramate CR as a phar-
macological adjunct in patients with type 2
or in combination with metformin.
besity and weight gain are major
nearly 90% of the population with
RESEARCH DESIGN AND
METHODS — This study was spon-
sored by Johnson & Johnson Pharmaceu-
tical Research & Development, LLC
(Raritan, NJ), conducted in accordance
with the Declaration of Helsinki and ICH
Good Clinical Practice, and approved by
ethics committees at all sites. All patients
provided full written informed consent
This study was performed at 22 outpa-
obese patients with type 2 diabetes treated
tion with metformin. Eligible patients had
BMI between 27 and 50 kg/m2, A1C 6.5–
11.0%, and fasting plasma glucose 7.0–
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
From the1Dallas Diabetes and Endocrine Center, Dallas, Texas;2Baylor Hospital, Dallas, Texas;3Duke
& Development, Raritan, New Jersey.
at Medical City, 7777 Forest Lane, C-685, Dallas, TX 75230. E-mail: email@example.com.
Received for publication 25 September 2007 and accepted in revised form 6 March 2007.
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.
HOMA, homeostasis model assessment; OGTT, oral glucose tolerance test.
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 Syste `me International (SI) units and conversion
factors for many substances.
© 2007 by the American Diabetes Association.
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.
E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s
O R I G I N A L A R T I C L E
DIABETES CARE, VOLUME 30, NUMBER 6, JUNE 2007
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