A Randomized Clinical Trial to Prevent Type 2 Diabetes

A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk

The DPP Research Group
Institutions and Investigators
Abbas Kitabchi
U. of Tennessee

Steven Kahn
U. of Washington
Edward Horton
Joslin Diabetes Center

Richard Hamman
U. of Colorado Health Sciences Center

Steven Haffner
U. of Texas Health Science Center and many others

* There is a long period of glucose intolerance that precedes the development of

diabetes
* Screening tests can identify persons at high risk
* There are safe, potentially effective interventions that can address modifiable risk

factors

Feasibility of Preventing
Type 2 Diabetes

Modifiable Risk Factors for
Type 2 Diabetes
* Obesity
* Body fat distribution
* Physical inactivity
* Elevated fasting and 2 hr glucose levels
* To prevent or delay the development of type 2 diabetes in persons with impaired

glucose tolerance (IGT)

DPP Primary Goal
DPP Secondary Goals
* Reduce cardiovascular disease (CVD) events
* Reduce CVD risk factors
* Reduce atherosclerosis

Study Design
* 3-group randomized clinical trial
* 27 clinical sites
* Standardized across clinics:
o Common protocol and procedures manual
o Staff training
o Data quality control program
Eligibility Criteria
Screening and Recruitment
Step 1 screening
Step 2 OGTT
Step 3 start run-in
Step 4 randomization
Number of participants
Step 3 end run-in

The DPP Research Group, Controlled Clin Trials (in press)
Study Interventions
Eligible participants
Randomized
Standard lifestyle recommendations
Intensive Metformin Placebo
Lifestyle
Primary Outcome: Diabetes

* Annual fasting plasma glucose (FPG) and 75 gm Oral Glucose Tolerance Test
o FPG > 126 mg/dL (7.0 mmol/L) or
o 2-hr > 200 mg/dL (11.0 mmol/L),
o Either confirmed with repeat test
* Semi-annual FPG
o > 126 mg/dL, confirmed

Lifestyle Intervention
An intensive program with the following specific goals:
* > 7% loss of body weight and maintenance of weight loss
o Dietary fat goal -- <25% of calories from fat
o Calorie intake goal -- 1200-1800 kcal/day
* > 150 minutes per week of physical activity

Lifestyle Intervention Structure
* 16 session core curriculum (over 24 weeks)
* Long-term maintenance program
* Supervised by a case manager
* Access to lifestyle support staff
o Dietitian
o Behavior counselor
o Exercise specialist

The Core Curriculum
* 16 session course conducted over 24 weeks
* Education and training in diet and exercise methods and behavior modification skills
* Emphasis on:
o Self monitoring techniques
o Problem solving
o Individualizing programs
o Self esteem, empowerment, and social support
o Frequent contact with case manager and DPP support staff

Post Core Program
* Self-monitoring and other behavioral strategies
* Monthly visits
o Must be seen in person at least every two months
* Supervised exercise sessions offered
* Periodic group classes and motivational campaigns
* Tool box strategies
o Provide exercise videotapes, pedometers
o Enroll in health club or cooking class

DPP Study Interventions:
Criteria for Drug Treatment
* Efficacy
* Safety
* Tolerability - minimal side effects
* Acceptability - dose frequency
Metformin- 850 mg per day escalating after
4 weeks to 850 mg twice per day
Placebo- Metformin placebo adjusted in
parallel with active drugs

Interventions:
Medications
DPP Population
Retention and Participation
Lifestyle Intervention: Physical Activity Results
Mean Change in Leisure Physical Activity
Placebo
Metformin
Lifestyle
Effect of Treatment on Incidence of Diabetes
Diabetes Incidence Rates by Age
Diabetes Incidence Rates by Ethnicity
Diabetes Incidence Rates by BMI
Body Mass Index (kg/m2)
Diabetes Incidence Rates by Fasting Glucose
Fasting Plasma Glucose: mg/dl (mmol/l)
Diabetes Incidence Rates by 2-hr Glucose
2-Hour Plasma Glucose (mg/dl)
Consistency of Treatment Effects
Normal Fasting Glucose
Placebo Metformin Lifestyle
Summary-1
* Both interventions were well accepted and safe
* Intensive lifestyle resulted in weight loss and increased activity level for the

duration of the study

Summary-2
* Both interventions were effective in men and women and all ethnic groups
* Intensive lifestyle intervention was effective in all age groups, including those > 60 years of age

Summary-3
* Intensive lifestyle intervention reduced the development of diabetes by 58%
* Metformin reduced the development of diabetes by 31%
* Lifestyle was more effective than metformin

Lipids by Sex and Ethnicity

A Randomized Clinical Trial to Prevent Type 2 Diabetes.ppt