Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release

Diabetes Care. 2014 Dec;37(12):3309-16. doi: 10.2337/dc14-0930. Epub 2014 Sep 23.

Abstract

Objective: Treatment algorithms for type 2 diabetes recommend weight loss for disease management. The safety and efficacy of treatment with phentermine (PHEN)/topiramate (TPM) extended release (ER) plus lifestyle modification for weight loss and glycemic benefits were assessed in two randomized, double-blind, placebo-controlled 56-week studies of obese/overweight adults with type 2 diabetes.

Research design and methods: The OB-202/DM-230 Study was a 56-week phase 2 trial that randomized subjects to receive once-daily placebo or PHEN/TPM ER 15 mg/92 mg (15/92). The primary end point was change in HbA₁c level. A post hoc analysis of a subpopulation with type 2 diabetes from a second study, CONQUER, is also presented. All subjects made lifestyle modifications, and comorbidities were managed to the standard of care.

Results: The study groups comprised 130 subjects with type 2 diabetes enrolled in the OB-202/DM-230 Study (mean baseline HbA₁c 8.7% [72 mmol/mol]) and 388 subjects with type 2 diabetes in the CONQUER Study (mean baseline HbA1c 6.8% [51 mmol/mol]). At week 56 in the OB-202/DM-230, change in weight (from intent-to-treat sample with last observation carried forward [ITT-LOCF]) was -2.7% for placebo and -9.4% for PHEN/TPM ER 15/92 (P < 0.0001 vs. placebo). Change in HbA1c level (from ITT-LOCF) was -1.2% (-13.1 mmol/mol) for placebo and -1.6% (-17.5 mmol/mol) for PHEN/TPM ER 15/92 (P = 0.0381). In both the OB-202/DM-230 and CONQUER, greater numbers of patients randomized to receive PHEN/TPM ER treatment achieved HbA₁c targets with reduced need for diabetic medications when compared with the placebo group. Common adverse events included paraesthesia, constipation, and insomnia.

Conclusions: PHEN/TPM ER plus lifestyle modification can effectively promote weight loss and improve glycemic control as a treatment approach in obese/overweight patients with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT00553787 NCT00600067.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Obesity Agents / administration & dosage*
  • Anti-Obesity Agents / adverse effects
  • Blood Glucose
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / therapy
  • Double-Blind Method
  • Female
  • Fructose / administration & dosage
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / therapy
  • Phentermine* / administration & dosage
  • Phentermine* / adverse effects
  • Topiramate
  • Treatment Outcome
  • Weight Loss* / drug effects

Substances

  • Anti-Obesity Agents
  • Blood Glucose
  • Delayed-Action Preparations
  • Topiramate
  • Fructose
  • Phentermine

Associated data

  • ClinicalTrials.gov/NCT00553787
  • ClinicalTrials.gov/NCT00600067