The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension

Tremblay, Angelo; Chaput, Jean‐Philippe; Bérubé-Parent, Sonia; Prud’homme, Denis; Leblanc, Claude; Alméras, Natalie; Després, Jean‐Pierre

doi:10.1007/s00228-006-0220-1

Cited by 53 publications

(35 citation statements)

References 22 publications

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“…It is currently not fully known how topiramate exerts its effect on body weight, but several mechanisms have been proposed (32). For example, studies have shown that topiramate decreases food intake in animals as well as in humans (8,33). Furthermore, animal studies showed that topiramate treatment can increase energy expenditure and decrease energetic efficiency (34,35).…”

Section: Adverse Eventmentioning

confidence: 99%

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

Sleddering

Snel

Streefland

et al. 2012

European Journal of Endocrinology

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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 36.6G1.3 kg/m 2 (meanGS.E.M.)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0G0.2) 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 b-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: 17.5G0.8 vs P: 18.5G1.0 mmol/kg LBM per min, tZ1.016, PZ0.33; step 2 (insulin infusion rate 40 mU/m 2 per min) T: 27.9G3.2 vs P: 28.8G1.9 mmol/kg LBM per min, tZ0.418, PZ0.68)). Subjects lost a small amount of weight during the topiramate period (T: K1.0G0.2 vs P: K0.1G0.2 kg, tZ2842, PZ0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. b-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0-10 min; T: 1929.6G265.7 vs P: 2024.7G333.6 pmol/l, tZK0.357, PZ0.73) and late (80-120 min; T: 28 017.7G5029.9 vs P: 31 567.7G5376.2 pmol/l, tZK1.481, PZ0.16) 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.

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Section: Adverse Eventmentioning

confidence: 99%

“…Furthermore, animal studies showed that topiramate treatment can increase energy expenditure and decrease energetic efficiency (34,35). This, however, was not demonstrated in humans (33). Why topiramate causes weight reduction in some patients but not in others is also up for debate.…”

Section: Adverse Eventmentioning

confidence: 99%

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

Sleddering

Snel

Streefland

et al. 2012

European Journal of Endocrinology

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“…Reduced hunger and appetite during weight loss could reflect cumulative anorectic effects of topiramate, balanced against the orexigenic effects of topiramate-promoted fat loss or related to energy deficit through other mechanisms. 27 This would favor persistence of weight loss. Regarding energy expenditure, topiramate might decrease energy storage and usage efficiency and thus increase energy expenditure.…”

Section: Topiramate (Tpm)mentioning

confidence: 99%

“…Regarding energy expenditure, topiramate might decrease energy storage and usage efficiency and thus increase energy expenditure. 27 Topiramate might inhibit adipocyte mitochondrial carbonic anhydrase isozyme V, 28 thereby inhibiting carbonic anhydrase-mediated lipogenesis. 29,30 Topiramate probably also affects lipoprotein lipase activity in white and brown adipose tissue, which would limit free fatty acid substrate for lipogenesis and may increase thermogenesis.…”

Section: Topiramate (Tpm)mentioning

confidence: 99%

A review of the metabolic effects of controlled-release Phentermine/Topiramate

Kiortsis¹

2013

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] obtained Food and Drug Administration (FDA) approval as an addition to a reduced-calorie diet and exercise for chronic weight management. Our aim was to review the available clinical evidence on weight loss, metabolic effects and adverse events associated with use of this product. MEtHODs: randomized controlled trials with phentermine/topiramate controlled-release were selected through a Medline search using the terms: phentermine and topiramate, phentermine and controlled release topiramate, new anti-obesity drugs and phentermine/topiramate, recent combinations of anti-obesity drugs and Qnexa ® . rEsULts: PHEN/tPM cr was associated with a weight loss of 8.1-10.9 % (mid and high dose, respectively), while patients in placebo groups lost 1.4-1.8 % of their initial weight. PHEN/tPM cr also resulted in a significant decrease of waist circumference. Weight loss with PHEN/tPM cr was associated with a decrease in blood pressure but with a slight increase in the heart rate. Furthermore, in all trials it exerted favorable effects on lipid profile, especially on triglycerides and high-density lipopoprotein (HDL) cholesterol. PHEN/tPM cr treatment also improved insulin sensitivity and glycemia. Moreover, it decreased significantly progression to type 2 diabetes. In all of the studies the severe adverse events were similar between the control groups and the groups of PHEN/tPM cr. the most frequent side-effects observed in the active treatment group were paresthesia, dysgeusia, dry mouth, constipation and insomnia. WHAt Is NEW AND cONcLUsION: PHEN/tPM cr combined with lifestyle modification may be an effective and well-tolerated treatment for obesity and weight-related metabolic complications. Its long-term efficacy and safety have yet to be defined.

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“…Sir, We read with great interest the paper of Tremblay and others [1] on topiramate's effect on weight, energy balance, appetite and satiety. They studied topiramate-induced weight loss (WL) in obese males who were, however, instructed not to start any diet or exercise program intended to induce WL during the course of the study.…”

mentioning

confidence: 99%

Topiramate-induced weight loss is possibly due to the blockade of conditioned and automatic processes

Khazaal

Zullino

2007

Eur J Clin Pharmacol

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The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension

Cited by 53 publications

References 22 publications

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

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

A review of the metabolic effects of controlled-release Phentermine/Topiramate

Topiramate-induced weight loss is possibly due to the blockade of conditioned and automatic processes

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