Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial.

OBJECTIVE

To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months.

DESIGN AND SUBJECTS

Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase).

MEASUREMENTS

Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion.

RESULTS

The mean age was 58.6+/-7.1 years, body weight 98.1+/-16.1 kg, BMI 33.0+/-4.5 kg/m(2), and glycosylated hemoglobin (HbA1c) 7.3+/-0.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.1+/-0.9%), fasting plasma glucose, body weight (-6.6+/-3.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate.

CONCLUSIONS

Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.