Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes
Article first published online: 4 AUG 2006
2006 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 9, Issue 3, pages 360–368, May 2007
How to Cite
Stenlöf, K., Rössner, S., Vercruysse, F., Kumar, A., Fitchet, M., Sjöström, L. and Study Group (2007), Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes. Diabetes, Obesity and Metabolism, 9: 360–368. doi: 10.1111/j.1463-1326.2006.00618.x
- Issue published online: 4 AUG 2006
- Article first published online: 4 AUG 2006
- Received 23 February 2006; accepted 19 March 2006
- glycaemic control;
- weight loss
Aim: The aim of this study was to examine the efficacy and safety of topiramate as an adjunct to diet and exercise in drug-naive, obese subjects with type 2 diabetes.
Methods: Drug-naive individuals with type 2 diabetes, body mass index (BMI) of ≥27 and <50 kg/m2 and haemoglobin A1c (HbA1c) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change®; Johnson & Johnson Healthcare Systems, Piscataway, NJ, USA) throughout the trial. After a 6-week placebo run-in, the subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Subjects were scheduled for 8-week titration and 52-week maintenance phases. The study was ended early; efficacy data were reported for a predefined modified intent-to-treat (MITT) population (n = 229), with 40 weeks of treatment. All the subjects who provided any safety data were included in the safety population (n = 535).
Results: Baseline mean weight was 103.7 kg, BMI 36 kg/m2 and HbA1c 6.7% across all treatment groups. By the end of week 40, the placebo, the topiramate 96 mg/day and topiramate 192 mg/day groups lost 2.5, 6.6 and 9.1% of their baseline body weight respectively (p < 0.001 vs. placebo, MITT population using last observation carried forward). The decrease in HbA1c was 0.2, 0.6 and 0.7% respectively (p < 0.001 vs. placebo, MITT). Topiramate significantly reduced blood pressure and urinary albumin excretion; a weight-loss-independent HbA1c improving effect of topiramate was demonstrated. Adverse events were predominantly related to central nervous system (CNS).
Conclusions: Topiramate as an add-on treatment to lifestyle improvements produced significant weight loss and improved glucose homeostasis in obese, drug-naive subjects with type 2 diabetes. These treatment advantages should be balanced against the occurrence of adverse events in the CNS.