Efficacy and safety of Topiramate in the treatment of obese subjects with essential hypertension
ABSTRACT The effect of topiramate on weight and blood pressure (BP) was examined in a randomized, placebo-controlled trial in obese subjects who had hypertension. After a 4-week, placebo, run-in period, 531 obese subjects (body mass index 27 to 50 kg/m(2)) who had established hypertension were randomly assigned to placebo or 96 or 192 mg/day of topiramate. All subjects received a standardized diet, exercise advice, and behavioral modification from run-in through study end. Initially scheduled for 60 weeks on medication, the sponsor ended the study early to develop a new controlled-release formulation. As a consequence, efficacy was assessed within a predefined modified intent-to-treat population (subjects who enrolled early enough to potentially complete 28 weeks on medication). The placebo and 96- and 192-mg groups had respective weight losses of 1.9%, 5.9%, and 6.5% from baseline (p <0.001 for each comparison with placebo) and decreases in diastolic BP of 2.1, 5.5, and 6.3 mm Hg (p <0.015 vs placebo). Systolic BP was decreased by 8.6 and 9.7 mm Hg in the 96- and 192-mg groups and 4.9 mm Hg in the placebo group (p = NS). Compared with placebo, the topiramate groups had larger proportions of subjects whose weight decreased by > or =5% and 10%, whose diastolic BP decreased by > or =5 and 10 mm Hg, and who achieved normalization of BP (BP <130/85 mm Hg). Adverse events included paresthesia, fatigue, taste perversion, loss of appetite, and difficulty with concentration and attention. In conclusion, topiramate produced clinically relevant effects in reducing body weight and BP, with generally mild to moderate adverse effects.
SourceAvailable from: Tania Markovic[Show abstract] [Hide abstract]
ABSTRACT: The US Food and Drug Administration (FDA) recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER) for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention.Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 01/2014; 7:35-44. DOI:10.2147/DMSO.S38979
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ABSTRACT: Weight loss can reduce the increased cardiovascular risk associated with obesity. Pharmacotherapy is a recognized weight loss treatment option; however, cardiovascular safety issues with some previous weight loss drugs raise concerns for newly approved pharmacotherapies. Phentermine is approved for short-term obesity treatment in conjunction with lifestyle modifications, but is commonly used chronically. Topiramate, approved for treating epilepsy and preventing migraines, also induces weight loss. A single-dose combination of low-dose phentermine and topiramate extended-release was recently approved by the United States Food and Drug Administration as an adjunct to lifestyle intervention for the chronic treatment of overweight/obese adults. This review summarizes and evaluates the cardiovascular risk/benefit profile associated with phentermine and topiramate, individually and in combination. Cardiovascular data associated with long-term use of phentermine and topiramate extended-release indicate that this combination may be a safe and effective option for reducing weight in overweight/obese patients at low-to-intermediate cardiovascular risk.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.Journal of Hypertension 03/2014; 32(6). DOI:10.1097/HJH.0000000000000145 · 4.22 Impact Factor
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ABSTRACT: Background. Medications for use as an adjunct to lifestyle modification therapy (LSM) for severe adolescent obesity are limited. Topiramate results in weight reduction in adults with obesity, but has not been studied in adolescents. Objective. To examine the effect of topiramate plus LSM on body mass index (BMI) reduction in adolescents with severe obesity. Methods. Data for this retrospective chart review were collected from patients attending a pediatric weight management program who were treated with LSM plus topiramate for 3 months minimum. Mean BMI percent change from baseline was evaluated using t-tests. Results. Twenty-eight patients (mean age 15.2 ± 2.5 years, mean baseline BMI 46.2 ± 10.3 kg/m(2)) were identified for inclusion. The 6-month percent change in BMI was -4.9, 95% confidence interval (-7.1, -2.8), P < .001. Conclusions. Topiramate with concurrent LSM was associated with clinically meaningful BMI reduction in adolescents with severe obesity. Randomized controlled clinical trials examining efficacy and safety of topiramate for severe obesity in adolescents are needed.Clinical Pediatrics 07/2014; 54(1). DOI:10.1177/0009922814542481 · 1.26 Impact Factor