Topiramate: Long-Term Maintenance of Weight Loss Induced by a Low-Calorie Diet in Obese Subjects

University of Milan, Milano, Lombardy, Italy
Obesity research (Impact Factor: 4.95). 10/2004; 12(10):1658-69. DOI: 10.1038/oby.2004.206
Source: PubMed


To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet.
Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination.
Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system.
During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.

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    • "ng anecdotal reports of weight loss occur - ring in patients with epilepsy , it was evaluated as a potential antiobesity drug in clinical trials [ Astrup et al . 2004a ] . Topiramate produced a very substantial weight reduction in subjects with obesity , particularly when administered after initial weight loss induced with a very low energy diet [ Astrup et al . 2004b ] , but an indica - tion as a monotherapy for obesity was aban - doned due to dose - dependent neuropsychiatric and cognitive adverse events , such as memory and concentration impairment , language diffi - culties and mood changes [ Nathan et al . 2011 ; Sommer et al . 2013 ] . Although the exact mecha - nism of action for weight loss w"
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    • "Several clinical studies showed that treatment with TPM is associated with significant weight loss of the patients, in contrast with the effects of traditional mood stabilizers generally leading to body weight gain [3] [4] [5] [6]. In a recent study following 307 obese subjects with type 2 diabetes over 1 year, TPM was effective for weight reduction and improvement in glycemic control [7]. "
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