Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects.
OBJECTIVE
To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Astrup
Arne
A
The Department of Human Nutrition and LMC, The Royal Veterinary and Agricultural University, 30 Rolighedsvej, 1958 Frederiksberg C, Copenhagen, Denmark. ast@kvl.dk
Caterson
Ian
I
Zelissen
Pierre
P
Guy-Grand
Bernard
B
Carruba
Michele
M
Levy
Brian
B
Sun
Xiang
X
Fitchet
Martin
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods*; D004038:Diet, Reducing; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy* / Q000517:prevention & control; D010292:Paresthesia / Q000139:chemically induced; D012449:Safety; D000077236:Topiramate; D016896:Treatment Outcome; D015431:Weight Loss
D019440:Anti-Obesity Agents; D000077236:Topiramate; D005632:Fructose