Phentermine and Topiramate for Patients with Dysglycemia

Chicago—Obese or overweight adults with dysglycemia who received phentermine and topiramate extended-release pills had a mean weight loss of 7.7% to 11.6% after 56 weeks of treatment, according to a post hoc analysis of a randomized, double-blind, phase 3 trial. The weight loss was consistent across all body mass index (BMI) categories and was associated with improvements in glycemic control.

Results were presented at the ADA meeting during a poster session. The poster was titled Weight Loss with Phentermine and Topiramate Extended-Release and Changes in Glycemic Parameters in Overweight and Obese Adults with Dysglycemia and Stratified By Baseline Body Mass Index.

The authors noted that the risk of type 2 diabetes increases with BMI. They added that the ADA recommends overweight or obese adults with prediabetes or type 2 diabetes lose weight to improve their glycemic control.

In July 2012, the FDA approved phentermine and topiramate extended-release to be used in combination with a reduced-calorie diet and exercise for chronic weight management. The oral medication is intended for obese adults (BMI ≥30 kg/m²) or overweight adults (BMI ≥27 kg/m²) with at least 1 weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.

In this study, the authors randomized 2487 overweight and obese adults with at least 2 weight-related comorbidities to receive placebo, 7.5-mg phentermine/46-mg topiramate, or 15-mg phentermine/92-mg topiramate once daily. Patients had a BMI between 27 kg/m² and 45 kg/m². The mean age of patients was 52.1 years, 67% were female, and 87% were white.

This analysis included the 1698 patients with dysglycemia, which the authors defined as a baseline fasting plasma glucose ≥100 mg/dL or blood glucose ≥100 mg/dL in the 2 hours following an oral glucose tolerance test.

In all BMI categories, patients in the phentermine and topiramate extended-release groups had a significant weight reduction compared with the placebo group (P<.0001 in all comparisons). For patients with a BMI <30 kg/m², mean weight loss at week 56 was 0.9% in the placebo group, 9.9% in the 7.5-mg phentermine/46-mg topiramate group, and 8.8% in the 15-mg phentermine/92-mg topiramate group. For patients with a BMI from ≥30 kg/m² to <35 kg/m², mean weight loss at week 56 was 2.3% in the placebo group, 7.7% in the 7.5-mg phentermine/46-mg topiramate group, and 10.4% in the 15-mg phentermine/92-mg topiramate group.

In addition, for patients with a BMI from ≥35 kg/m² to <40 kg/m², mean weight loss at week 56 was 2.3% in the placebo group, 8.8% in the 7.5-mg phentermine/46-mg topiramate group, and 10.2% in the 15-mg phentermine/92-mg topiramate group. For patients with BMI ≥40 kg/m², mean weight loss at week 56 was 2.7% in the placebo group, 8.4% in the 7.5-mg phentermine/46-mg topiramate group, and 11.6% in the 15-mg phentermine/92-mg topiramate group.

The most common treatment-related adverse events for patients taking phentermine and topiramate extended-release pills were paresthesia, dry mouth, constipation, dizziness, insomnia, dysgeusia, and nausea. In addition, 8% of patients in the placebo group, 11% of patients in the 7.5-mg phentermine/46-mg topiramate group, and 19% of patients in the 15-mg phentermine/92-mg topiramate group had a treatment-related adverse event that led to discontinuation. Fewer than 1% of patients in the phentermine and topiramate extended-release groups had hypoglycemia, but none of the events were considered severe, according to the authors.

VIVUS Inc. supported this study.