A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Topiramate Controlled-Release in the Treatment of Obese, Type 2 Diabetic Patients

Abstract

Objective: This is a randomized, placebo-controlled study of the weight loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes, treated with diet and exercise alone, or in combination with metformin.

Research Design and Methods: Patients with type 2 diabetes, BMI ≥27, with HbA_1c >6.5% and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/d. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.

Results: A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 kg and 6.0 kg, which represented 2.3% and 5.8%, respectively, of their baseline body weight (P<0.001 vs placebo). HbA_1c improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1% and 6.7% respectively, representing a 0.4%, and 0.9% reduction from baseline (P<0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric, or central and peripheral nervous system-related.

Conclusion: Topiramate CR treatment produced significant weight loss and meaningful improvements in HbA_1c and blood pressure in obese patients with type 2 diabetes mellitus treated with diet and exercise or in combination with metformin. However, the CNS and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.

Conclusion: The study has been registered at www.ClinicalTrials.gov, identifier NCT00231647.