Short-term topiramate treatment does not improve insulin sensitivity or secretion in obese insulin-resistant women

Abstract

Objective: Long-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss.

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: Low-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.