Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy

Ben‐Menachem, Elinor; Axelsen, Mette; Johanson, Else Hellebö; Stagge, Anna; Smith, Ulf

doi:10.1038/oby.2003.78

Cited by 180 publications

(127 citation statements)

References 17 publications

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“…In animal studies, topiramate has been shown to have an insulin-sensitizing effect (6,8); however, whether this is the case in humans is currently still under debate. Studies in obese subjects have shown that long-term topiramate treatment (24-60 weeks, 64-384 mg/day) leads to significant weight loss (2,3,4) and reduces glucose levels in obese patients with epilepsy (25,26,27). Furthermore, topiramate treatment (16-40 weeks, 96-192 mg/day) causes a significant decrease in HbA1c in T2DM patients (9,10,11).…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…However, recent reports have shown that overweight non-diabetic patients experience significant weight reduction on topiramate treatment. [4][5][6][7] Interestingly, recent studies in animal models of obesity and diabetes have shown that insulin sensitivity is improved by topiramate even before the weight reduction. 8 The mechanism(s) for this is unclear, but recent studies suggested that the adipose tissue might be the target for such an effect in the animal models.…”

Section: Introductionmentioning

confidence: 99%

Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial

et al. 2007

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Objective: To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months. Design and subjects: Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebocontrolled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase). Measurements: Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion. Results: The mean age was 58.677.1 years, body weight 98.1716.1 kg, BMI 33.074.5 kg/m 2 , and glycosylated hemoglobin (HbA1c) 7.370.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.170.9%), fasting plasma glucose, body weight (À6.673.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate. Conclusions: Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

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“…Por outro lado, perda de peso tem sido relatada por 2% a 75% dos pacientes em uso de felbamato, 10% a 20% dos usuários de topiramato e em um número não estabelecido de indivíduos em tratamento com zonisamida (22)(23)(24)(25). O felbamato levou à perda de 3% a 5% do peso corporal em crianças, notadamente nos primeiros meses de tratamento, porém mais estudos necessitam ser realizados, principalmente em adultos, para que se entendam melhor os efeitos dessa droga no peso corporal (22).…”

Section: Efeitos Das Dae Sobre O Peso Corporalunclassified

“…O felbamato levou à perda de 3% a 5% do peso corporal em crianças, notadamente nos primeiros meses de tratamento, porém mais estudos necessitam ser realizados, principalmente em adultos, para que se entendam melhor os efeitos dessa droga no peso corporal (22). Com o topiramato, a redução média de peso é de 4,2 kg (4,3% do peso inicial) no terceiro mês de tratamento e 10,9 kg (11% do peso inicial) após um ano (23). Acredita-se que esse efeito do topiramato se deva ao antagonismo dos receptores glutaminérgicos.…”

Section: Efeitos Das Dae Sobre O Peso Corporalunclassified

“…Acredita-se que esse efeito do topiramato se deva ao antagonismo dos receptores glutaminérgicos. Entretanto, em protocolos clínicos com o topiramato, a tolerabilidade dos pacientes às doses que resultam em redução ponderal foi ruim, com 20% a 30% de abandono do tratamento por efeitos colaterais, especialmente parestesias, lentificação cognitiva e nervosismo (23,24). Um estudo duplo-cego e controlado foi realizado com a zonisamida, verificandose uma perda de peso de 6% com a droga após 16 semanas, em comparação a uma perda de 1% do grupo placebo (25).…”

Section: Efeitos Das Dae Sobre O Peso Corporalunclassified

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Efeitos endócrinos e metabólicos das drogas antiepilépticas

Bortolini

Kulak

Borba

et al. 2009

Arq Bras Endocrinol Metab

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RESUMOAs drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo -tanto no tratamento das epilepsias como para outros fins -frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética. Arq Bras Endocrinol Metab. 2009;53(7):795-803.Descritores Drogas antiepilépticas; epilepsia; metabolismo mineral ósseo; obesidade; disfunção gonadal; disfunção tireoideana. ABSTRACTThe antiepileptic drugs (AED) have been widely used for a great deal of people -in the treatment of epilepsy and other diseases -throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy. INTRODUÇÃO A s drogas antiepilépticas (DAE) são utilizadas no tratamento da epilepsia desde 1857, quando Locock usou sal de brometo com resultados positivos em mulheres com epilepsia catamenial (1). Desde então, inúmeros medicamentos foram introduzidos na prática clínica para o tratamento dos mais diversos tipos de epilepsia, uma doença crônica comum que atinge homens e mulheres em todas as faixas etárias, com incidência anual de 43 casos por 100 mil habitantes em países indus trializados e o dobro em países em desenvolvimento (2). No Brasil, a prevalência encontrada tem variado de 0,4% a 0,8% da população (3). Além do clássico uso para tratamento da epilepsia, as várias ações das DAE resultaram em uma ampliação de seu uso terapêutico e, hoje, elas são empregadas tanto no controle de desordens psiquiátricas, como ansiedade, esquizofrenia e transtorno bipolar, como em distúrbios neurológicos diversos, incluin do tremor essencial, cefaleia e dores neuropáticas (4). Em caráter experimental, as DAE têm sido testadas em pacientes com câncer e infecção por HIV, no tratamento para o abuso de drogas e álcool e, também, como agentes neuroprotetores (4).Os principais mecanismos de ação das DAE mais utilizadas incluem bloqueio dos canais de sódio ou de cálcio dependentes de voltagem, aumento da inibição mediada por GABA e bloqueio ao glutamato (5). A fenitoína, o fenobarbital e a carbamazepina são metabolizados por via hepática por meio do citocromo P450 ("drogas indutoras hepáticas"), ao passo que a enzima hepática uridina difosfato glucuronosil transferase (UGP) é responsável pela metabolização do valproato

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Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy

Cited by 180 publications

References 17 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

Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial

Efeitos endócrinos e metabólicos das drogas antiepilépticas

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