Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Diabetes Mellitus, Type 2

Diabetes Mellitus

Obesity

Prediabetic State

Glucose Intolerance

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Metformin

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

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.

randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2

DPPOS Group Lifestyle

Administered as 850mg twice per day, masked in DPP and open label in DPPOS

In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.

DPPOS Boost Lifestyle

16 session curriculum in group format. In DPP delivered to ILS as individual sessions

Intensive Lifestyle Group Session

David M. Nathan, MD

Marinella Temprosa, PhD

Barbara Linder, MD, PhD

Kishore Gadde, MD

David Ehrmann, MD

Kevin Furlong, MD

Kathleen Jablonski, PhD

Ronald B Goldberg, MD

Helen P Hazuda, MD

Dana Dabelea, MD, PhD

Medha Munshi, MD

Steven Kahn, MB, ChB

Samuel Dagogo-Jack, MD, MB

Mark Molitch, MD

Happy Araneta, PhD,MPH

F. Xavier Pi-Sunyer, MD

Kieren J Mather, MD

Michelle Magee, MD

Karol E Watson, MD

Angela Brown, MD

Sherita Hill Golden, MD, MHS

David S Schade, MD

Jill Crandall, MD

Elizabeth Venditti, PhD

Marjerie Mau, MD

William Knowler, MD

Santica M Marcovina, PhD

David M Nathan, MD

Christine Lee, MD

Sunder Mudaliar, MD

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.

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

Diabetes Prevention Program Outcomes Study

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository

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).

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).

All primary incident cancers except non-melanoma skin cancer

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.

Measured using coronary artery calcification (CAC).

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 ).

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.

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.

All cause-mortality through clinic reports and National Death Index search

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Aging (NIA)

National Institute on Minority Health and Health Disparities (NIMHD)

National Heart, Lung, and Blood Institute (NHLBI)

National Cancer Institute (NCI)

National Eye Institute (NEI)

National Center for Research Resources (NCRR)

Office of Research on Women's Health (ORWH)

Centers for Disease Control and Prevention

American Diabetes Association

Indian Health Service

General Clinical Research Program

US Department of Veterans Affairs

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Boost / Lifestyle, previously Intensive Lifestyle during the DPP

Group Lifestyle: Quarterly group lifestyle sessions

Boost Lifestyle: In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.

1 Original Lifestyle

Metformin / Lifestyle, previously the metformin treatment group during DPP

Group Lifestyle: Quarterly group lifestyle sessions

Metformin: Administered as 850mg twice per day

2 Original Metformin

Group Lifestyle, previously placebo treated participants during DPP

Group Lifestyle: Quarterly group lifestyle sessions

3 Original Placebo

randomized to unmasked Intensive Lifestyle (ILS) during the DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle plus DPPOS Boost Lifestyle sessions in DPPOS Phase 1 and 2

DPPOS Group Lifestyle: Quarterly group lifestyle sessions

DPPOS Boost Lifestyle: In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.

Intensive Lifestyle Group Session: 16 session curriculum in group format. In DPP delivered to ILS as individual sessions

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.

DPPOS Group Lifestyle: Quarterly group lifestyle sessions

Metformin: Administered as 850mg twice per day, masked in DPP and open label in DPPOS

Intensive Lifestyle Group Session: 16 session curriculum in group format. In DPP delivered to ILS as individual sessions

randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2

DPPOS Group Lifestyle: Quarterly group lifestyle sessions

Intensive Lifestyle Group Session: 16 session curriculum in group format. In DPP delivered to ILS as individual sessions

Total

An additional 3 participants were enrolled after publication

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Marinella Temprosa, PI of Coordinating Center

Development of Diabetes.

Number with microvascular outcome data and included in the primary outcome analysis

Prevalence of Aggregate Microvascular Complication

Total Cancer Except Non-melanoma Skin Cancer

Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)

Women

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

DPPOS Group Lifestyle: Quarterly group lifestyle sessions

DPPOS Boost Lifestyle: In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.

Intensive Lifestyle Group Session: 16 session curriculum in group format. In DPP delivered to ILS as individual sessions

DPPOS Participants who met eligibility criteria and consented to have CAC measurements - by sex

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