Source: DGNews  |  Posted 8 years ago

By Jill Stein

PARIS, FRANCE -- August 26, 2003 -- Topiramate, used in combination with an intensive behavioural intervention, seems to be safe and effective for weight reduction in newly diagnosed obese, type 2 diabetics who are following a controlled diet.

Topiramate is a sulfamate-substituted monosaccharide shown to promote weight loss in non-diabetic, obese subjects in a 6-month, dose-ranging trial.

Dr. Kaj Stenlof, with Pennington Management of Clinical Trials in Baton Rouge, Louisiana, United States, and colleagues elsewhere, randomised 541 patients to 60 weeks' treatment with topiramate 96 mg/d or 192 mg/d, or placebo, following a six-week placebo run-in period. The study was conducted at 20 centres in Sweden. The results were reported on August 25th at the Eighteenth International Diabetes Federation (IDF) Congress.

The sponsor terminated the study prematurely in order to develop an improved formulation with the potential for enhanced tolerability in this population; as such, no patient completed the 52-week maintenance phase.

Patients on topiramate were titrated up to their treated dose over the course of 4 to 6 weeks depending on their target dose. All participants were maintained on a 600 kcal deficit diet, exercise, and behavioural modification throughout the trial.

Efficacy was assessed in the 241 patients who completed at least 40 weeks of treatment.

Analysis at 40 weeks shows that the two topiramate groups had significantly greater mean percent weight loss and decreases in haemoglobin A1 C levels than the placebo group. The percent change in body weight was -6.6% in the lower dose topiramate group, -9.1% in the higher dose topiramate group, and -2.5% in the placebo group. The change in haemoglobin A1C at 40 weeks was -0.6, -0.7, and -0.2% in the three groups, respectively.

A higher percentage of patients in the topiramate groups versus the placebo group achieved at least a 5 or 10% weight loss. A higher proportion of topiramate-treated patients also achieved at least a 0.5, 0.7, and 1% decrease in haemoglobin A1 C levels.

The most common treatment-related adverse events were related to the central nervous system and included paraesthesia, fatigue, hypoesthesia, injury, and abnormal vision. The most common adverse events resulting in withdrawal were paraesthesia in 5% of patients, depression in 3%, and difficulty with memory in 3%.

"Our results show that using topiramate to treat obese patients with well-controlled, drug-na