Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes

Diabetes Obes Metab. 2007 May;9(3):360-8. doi: 10.1111/j.1463-1326.2006.00618.x.

Abstract

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 > or =27 and <50 kg/m(2) and haemoglobin A(1c) (HbA(1c)) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change((R)); 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/m(2) and HbA(1c) 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 HbA(1c) 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 HbA(1c) 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / complications
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Type 2 / complications*
  • Double-Blind Method
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Glycated Hemoglobin A / analysis
  • Humans
  • Lipid Metabolism / drug effects
  • Male
  • Middle Aged
  • Nervous System Diseases / chemically induced
  • Obesity / complications
  • Obesity / drug therapy*
  • Topiramate
  • Treatment Outcome
  • Weight Loss / drug effects

Substances

  • Anti-Obesity Agents
  • Blood Glucose
  • Glycated Hemoglobin A
  • Topiramate
  • Fructose