Cardiometabolic Disease Staging Predicts Effectiveness of Weight-Loss Therapy to Prevent Type 2 Diabetes: Pooled Results From Phase III Clinical Trials Assessing Phentermine/Topiramate Extended Release

Diabetes Care. 2017 Jul;40(7):856-862. doi: 10.2337/dc17-0088. Epub 2017 Apr 28.


Objective: To assess the ability of medication-assisted weight loss to prevent diabetes as a function of the baseline weighted Cardiometabolic Disease Staging (CMDS) score.

Research design and methods: We pooled data from 3,040 overweight and obese participants in three randomized controlled trials-CONQUER, EQUIP, and SEQUEL-assessing efficacy and safety of phentermine/topiramate extended release (ER) for weight loss. In these double-blind phase III trials, overweight/obese adult patients were treated with a lifestyle intervention and randomly assigned to placebo versus once-daily oral phentermine/topiramate ER. The weighted CMDS score was calculated using baseline quantitative clinical data including waist circumference, blood glucose, blood pressure, and blood lipids. Incident diabetes was defined based on serial measures of fasting glucose, 2-h oral glucose tolerance test glucose, and/or HbA1c.

Results: The absolute decrease in 1-year diabetes incidence rates in subjects treated with medication versus placebo was greatest in those with high-risk CMDS scores at baseline (10.43-6.29%), intermediate in those with moderate CMDS risk (4.67-2.37%), and small in the low-risk category (1.51-0.67%). The number of participants needed to treat to prevent one new case of diabetes over a 56-week period was 24, 43, and 120 in those with baseline CMDS scores of ≥60, 30-59, and 0-29, respectively.

Conclusions: Numbers needed to treat to prevent one case of type 2 diabetes are markedly lower in patients with high-risk scores. CMDS can be used to quantify risk of diabetes in overweight/obese individuals and predict the effectiveness of weight-loss therapy to prevent diabetes.

Trial registration: NCT00553787 NCT00554216 NCT00796367.

MeSH terms

  • Adult
  • Anti-Obesity Agents / administration & dosage*
  • Blood Glucose
  • Clinical Trials, Phase III as Topic
  • Delayed-Action Preparations / administration & dosage
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Double-Blind Method
  • Female
  • Fructose / administration & dosage
  • Fructose / analogs & derivatives*
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / complications
  • Obesity / drug therapy*
  • Phentermine / administration & dosage*
  • Topiramate
  • Waist Circumference
  • Weight Loss


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

Associated data