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

Abstract

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 placebocontrolled 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 58.677.1 years, body weight 98.1716.1 kg, BMI 33.074.5 kg/m 2 , and glycosylated hemoglobin (HbA1c) 7.370.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.170.9%), fasting plasma glucose, body weight (À6.673.3%), 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.

Short-term topiramate treatment does not improve insulin sensitivity or secretion in obese insulin-resistant women

“…In addition, Li et al (28) observed no differences in HOMA-IR after 6 months of topiramate treatment in children with epilepsy (median dosage 2.15 mg/kg/day). In a study of Eliasson et al (29) in T2DM patients, an improvement in insulin-stimulated glucose disposal (using a hyperinsulinemic euglycemic clamp) could not be detected after 11 months of topiramate treatment (192 mg/day), despite a significant decrease in body weight, fasting plasma glucose, and HbA1c. A trend in enhanced hepatic insulin sensitivity was observed, but this difference did not reach statistical significance, perhaps because of the limited sample size and the relatively high-insulin infusion rate (1 mU/kg per min), which might be expected to suppress hepatic glucose production almost completely.…”

Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization

“…We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a robust reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to CCK-8 and associated reduction of meal size. In contrast to other anti-obesogenic therapies, including melanocortin receptor ligands [MTII (72), BIM-22493 (46)], topiramate (27), and the GLP-1 receptor agonist, liraglutide (50), which reduce both fat mass and lean mass, oxytocin is one of the few hormones that we are aware of [aside from leptin (36,41,69)] that protects against the loss in lean mass and selectively reduces fat mass, thus highlighting its translational potential. Combined with our evidence that chronic subcutaneous infusions of oxytocin are sufficient to reduce body weight gain in animals maintained on a HFD at a dose that does not appear to elicit aversive behavioral responses (e.g., nausea or malaise), these findings identify oxytocin as a viable agent for obesity prevention and treatment.…”

Anthropometric indexes, insulin resistance, and serum leptin and lipid levels in women with cryptogenic epilepsy receiving topiramate treatment

“…This finding is concordant with the recent data suggesting meaningful improvements in glycemic control parameters after topiramate treatment. 10,[16][17][18][19] Although reduction of waist circumference can be associated with weight reduction, there is no unequivocal report regarding whether topiramate's effects on glycemic parameters are dependent on its weight loss effects. Therefore, contrary to the reduction in waist circumference, the improvement in insulin resistance may not be directly attributed to the weight loss effects of topiramate, according to the available data.…”