Efficacy and Safety of Topiramate in the Treatment of Obese Subjects With Essential Hypertension

University of Oslo, Oslo, Norway.
The American Journal of Cardiology (Impact Factor: 3.28). 07/2005; 96(2):243-51. DOI: 10.1016/j.amjcard.2005.03.053
Source: PubMed


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.

12 Reads
    • "It is recommended that moderate weight loss in obese diabetic patients can lower serum glucose and lessen the amount of insulin needed.[3] 5-10% weight loss in obese patients can reduce blood pressure in all individuals and can lessen the need for hypertension drugs in mild to moderate hypertensive patients.[4] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has been associated with several co-morbidities such as diabetes and increased mortality. In general, the use of medication promotes only a modest weight loss in the range of 2 to 10 kg, usually most effective during the first 6 months of therapy; however, studies have shown positive effects on other risk factors such as blood pressure and serum glucose levels, but there are fewer studies in patients with diabetes. The aim of this study was to assess the effect of topiramate on weight reduction patients with type 2 diabetes. This was a 32-week randomized clinical trial study of 69 subjects during 2008-2010. Patients, in two treatment groups were given topiramate (39 patients) and Placebo (30 patients) and were subjected to participation in a non-pharmacologic lifestyle intervention program; which were randomly allocated in our two groups. The percentage change in body weight and Body Mass Index (BMI) at the end of the study was the primary efficacy endpoint and secondary indicators were changes in blood pressure (BP), proportion of subjects who achieved 5% or 10% weight loss, changes in lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides); and changes in glycosylated hemoglobin (HgA1c). Paired samples and independent samples t-test was used for statistical analysis. (RCT code: IRCT201112036027N2). All results were extracted on base of 69 (Intended to treat) ITT patients. Mean BMI changes was significantly higher in patients treated with topiramate (-1.08 1.90 vs. +0.086 ± 1.05 kg/m², P = 0.006). Mean weight loss percentage was significantly different between active and placebo groups (-3.02 ± 5.78% vs. +0.32 ± 3.54%, P = 0.005) and systolic blood pressure and HgA1C significantly decreased in patients treated with topiramate (P = 0.021 and P = 0.047, respectively). Topiramate induced weight loss and improved glycemic control in obese, diabetic patients.
    Journal of research in medical sciences 04/2013; 18(4):297-302. · 0.65 Impact Factor
  • Source
    • "Topiramate has consistently decreased the efficacy of energy utilization in animal models, and effects on food consumption have varied with the model. These effects on energy efficiency may be mediated by stimulation of lipoprotein lipase in brown adipose tissue and skeletal muscle, thus increasing thermogenesis (10) or increasing the expression of uncoupling proteins 2 and 3 [49], thus directly decreasing the efficiency of energy utilization [51]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis.
    PLoS ONE 05/2012; 7(5):e37757. DOI:10.1371/journal.pone.0037757 · 3.23 Impact Factor

Show more

Similar Publications