Toplak H et al. (2007) Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Int J Obes (Lond) 31: 138–146

The anticonvulsant topiramate causes dose-dependent weight loss in humans and in animal models of diabetes. Toplak and colleagues, therefore, investigated the efficacy and safety of topiramate as an antiobesity medication in patients with diabetes.

This international, randomized, double-blind, placebo-controlled trial included 640 obese patients (BMI 27–50 kg/m2) with type 2 diabetes. All patients continued metformin monotherapy and participated in a lifestyle-intervention program (hypocaloric diet, exercise and advice). After a 6 week placebo treatment period, patients were randomly allocated to receive placebo (n = 208), topiramate 96 mg (n = 219), or topiramate 192 mg (n = 213) daily. About 80% of participants reached the target doses. The study was terminated early because the sponsor switched funding to development of controlled-release topiramate.

After 24 weeks, weight losses of 4.5% and 6.5% were achieved in patients who received 96 mg and 192 mg topiramate daily, respectively, compared with 1.7% in placebo-treated patients (P <0.001 for both comparisons). Glycated hemoglobin levels and systolic blood pressure improved in topiramate-treated patients. Weight loss continued in patients who continued topiramate therapy beyond 24 weeks. More topiramate-treated than placebo-treated patients withdrew owing to intolerable adverse events (13% versus 7%); most withdrawals were related to cognitive or neurological symptoms and fatigue, and occurred in patients given the highest topiramate dose.

The authors assert that topiramate is an effective antiobesity medication in obese patients with diabetes, and also improves patients' glycemic control; however, these results require confirmation.