Abstract | OBJECTIVE: DESIGN: Randomized, double-blind, crossover, placebo-controlled study. METHODS: Thirteen obese (BMI 36.6 ± 1.3 kg/m(2) (mean ± s.e.m.)), insulin-resistant (homeostasis model of assessment- insulin resistance 2.0 ± 0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp. RESULTS: Hepatic and peripheral insulin sensitivities were not affected by topiramate treatment ( glucose disposal rate (step 1 ( insulin infusion rate 10 MU/M(2) per min) T: 17.5 ± 0.8 vs P: 18.5 ± 1.0 μmol/kg(LBM) per min, t=1.016, P=0.33; step 2 ( insulin infusion rate 40 mU/m(2) per min) T: 27.9 ± 3.2 vs P: 28.8 ± 1.9 μmol/kg(LBM) per min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the topiramate period (T: -1.0 ± 0.2 vs P: -0.1 ± 0.2 kg, t=2842, P=0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0-10 min; T: 1929.6 ± 265.7 vs P: 2024.7 ± 333.6 pmol/l, t=-0.357, P=0.73) and late (80-120 min; T: 28,017.7 ± 5029.9 vs P: 31,567.7 ± 5376.2 pmol/l, t=-1.481, P=0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems. CONCLUSIONS:
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Authors | Maria A Sleddering, Marieke Snel, Trea C M Streefland, Hanno Pijl, Ingrid M Jazet |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 167
Issue 6
Pg. 839-45
(Dec 2012)
ISSN: 1479-683X [Electronic] England |
PMID | 22983924
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Obesity Agents
- Insulin
- Topiramate
- Fructose
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Topics |
- Adolescent
- Adult
- Aged
- Anti-Obesity Agents
(therapeutic use)
- Double-Blind Method
- Female
- Fructose
(analogs & derivatives, therapeutic use)
- Humans
- Insulin
(metabolism)
- Insulin Resistance
(physiology)
- Insulin Secretion
- Middle Aged
- Obesity
(drug therapy, metabolism)
- Topiramate
- Young Adult
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