Diabetes Prevention Program Outcomes Study

Study Overview
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Brief Summary
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The Diabetes Prevention Program (DPP) was a multi-center trial examining the ability of an intensive lifestyle or metformin to prevent or delay the development of diabetes in a high risk population due to the presence of impaired glucose tolerance (IGT, 2 hour glucose of 140-199 mg/dl). The DPP has ended early demonstrating that lifestyle reduced diabetes onset by 58% and metformin reduced diabetes onset by 31%. DPPOS (2002-2013) is designed to take advantage of the scientifically and clinically valuable DPP participants. This group of participants is nearly 50% minority and represents the largest at risk population ever studied. Clinically important research questions remain that focus on 1) durability of the prior DPP intervention, 2) determination of the clinical course of precisely known new onset diabetes, in particular regarding microvascular disease, CVD risk factors and atherosclerosis, 3) close examination of these topics in men vs women and in minority populations. The major aims of DPPOS-3 (2014-2025) take advantage of the long-term randomized exposure of the study cohort to metformin and the aging of the DPPOS cohort. The metformin exposure and high degree of study retention and adherence ( 85% of the DPPOS cohort continues to attend annual and mid-year visits) allows DPPOS-3 to examine the long-term effects of metformin on cardiovascular disease (CVD) and cancer outcomes, outcomes of great clinical interest and import.

Detailed Description
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The current DPPOS Executive Summary and protocol, as well as DPPOS protocol and lifestyle manuals and publications are available at: http://www.dppos.org

Official Title
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Diabetes Prevention Program Outcomes Study

Conditions
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Diabetes Mellitus, Cancer, CVD

Intervention / Treatment
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* Behavioral: DPPOS Group Lifestyle
* Drug: Metformin
* Behavioral: DPPOS Boost Lifestyle
* Behavioral: Intensive Lifestyle Group Session


Participation Criteria
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Eligibility Criteria
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Participation as a volunteer in the Diabetes Prevention Program (DPP).

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Original Lifestyle<br>randomized to unmasked Intensive Lifestyle during the DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle plus DPPOS Boost Lifestyle sessions in DPPOS Phase 1 and 2 | Behavioral: DPPOS Group Lifestyle<br>* Quarterly group lifestyle sessions<br>Behavioral: DPPOS Boost Lifestyle<br>* In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.<br>Behavioral: Intensive Lifestyle Group Session<br>* 16 session curriculum in group format. In DPP delivered to ILS as individual sessions<br>* Other names: Intensive lifestyle session (ILS);|
| Active Comparator: 2 Original Metformin<br>randomized to the masked metformin treatment group during DPP and continued open label in DPPOS. Participants were also offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2. | Behavioral: DPPOS Group Lifestyle<br>* Quarterly group lifestyle sessions<br>Drug: Metformin<br>* Administered as 850mg twice per day, masked in DPP and open label in DPPOS<br>* Other names: Glucophage;Behavioral: Intensive Lifestyle Group Session<br>* 16 session curriculum in group format. In DPP delivered to ILS as individual sessions<br>* Other names: Intensive lifestyle session (ILS);|
| Placebo Comparator: 3 Original Placebo<br>randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2 | Behavioral: DPPOS Group Lifestyle<br>* Quarterly group lifestyle sessions<br>Behavioral: Intensive Lifestyle Group Session<br>* 16 session curriculum in group format. In DPP delivered to ILS as individual sessions<br>* Other names: Intensive lifestyle session (ILS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Diabetes. | Primary outcome for years 2002-2008 defined according to American Diabetes Association criteria (fasting plasma glucose level >= 126 mg/dL [7.0 mmol/L] or 2-hour plasma glucose >= 200 mg/dL [11.1 mmol/L], after a 75 gram oral glucose tolerance test (OGTT), and confirmed with a repeat test). | Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP). | 
| Prevalence of Aggregate Microvascular Complication | Aggregate microvascular disease is defined as the average prevalence of 3 components: (1) retinopathy measured by photography (ETDRS of 20 or greater); (2) neuropathy detected by Semmes Weinstein 10 gram monofilament, and (3) nephropathy based on estimated glomerular filtration rate (eGFR by chronic kidney disease (CKD-Epi) equation ) (<45 ml/min, confirmed) and albumin-to-creatinine ratio in spot urine (> 30mg/gm, confirmed). | Outcomes were assessed from 2012-2013 (approximately 2 years). | 
| Total Cancer Except Non-melanoma Skin Cancer | All primary incident cancers except non-melanoma skin cancer | Outcomes were assessed from 1996-2020 (approximately 24 years). | 
| Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD) | Defined as MI, stroke and CVD death. These outcomes were collected since randomization and adjudicated by an outcomes committee who are blinded to treatment assignment. | Outcomes were assessed from 1996-2025 (approximately 29 years). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subclinical Atherosclerosis | Measured using coronary artery calcification (CAC). | Outcomes were assessed from 2012-2013 (approximately 2 years). | 
| Cognitive Function | Cognitive function defined as a composite measure constructed from tests of memory (English Spanish Verbal Learning Test) and executive function (word fluency and Digit Symbol Substitution Test ). | Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020. | 
| Short Physical Performance Battery | Physical function is measured using the short physical performance battery (SPPB), which is comprised of measures of 1) time to walk 3-4 meters, 2) balance, i.e., side-by-side stand, semi-tandem stand, and tandem stand, and 3) repeated chair stands. | Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020. | 
| Frailty | Description: The Cardiovascular Health Study Frailty score is based on 5 frailty characteristics: slow walking speed, low energy expenditure, exhaustion, weak grip strength, and unintentional weight loss. | Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020. | 
| Mortality | All cause-mortality through clinic reports and National Death Index search | Outcomes were assessed throughout follow-up from 1996 to 2022. National Death Index search conducted in 2019 using early release data as of Dec 2018. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, DPP, IGT, Prediabetes, Type 2 diabetes, Macrovascular disease, Microvascular disease, Lifestyle, Metformin