title: 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.
authors: University of Oslo, Oslo, Norway. serena.tonstad@uus.no
authors: Serena
authors: S
authors: Tonstad
authors: Andrzej
authors: A
authors: Tykarski
authors: Joshua
authors: J
authors: Weissgarten
authors: Alla
authors: A
authors: Ivleva
authors: Brian
authors: B
authors: Levy
authors: Ashish
authors: A
authors: Kumar
authors: Martin
authors: M
authors: Fitchet
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D000077236:Topiramate; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D019440:Anti-Obesity Agents; D000077236:Topiramate; D005632:Fructose