Diabetes Prevention Program Outcomes Study

Phase 3

Active, not recruiting

Conditions: Diabetes Mellitus
CVD
Cancer

Interventions: Behavioral: DPPOS Group Lifestyle
Behavioral: DPPOS Boost Lifestyle
Drug: Metformin
Behavioral: Intensive Lifestyle Group Session

Registration Number: NCT00038727

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 2779

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1 Original Lifestyle	DPPOS Group Lifestyle	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
1 Original Lifestyle	DPPOS Boost Lifestyle	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
1 Original Lifestyle	Intensive Lifestyle Group Session	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
2 Original Metformin	DPPOS Group Lifestyle	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.
2 Original Metformin	Intensive Lifestyle Group Session	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.
3 Original Placebo	DPPOS Group Lifestyle	randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2
3 Original Placebo	Intensive Lifestyle Group Session	randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2
2 Original Metformin	Metformin	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.

Primary Outcome Measures

Name	Time	Method
Development of Diabetes.	Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP).	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).
Prevalence of Aggregate Microvascular Complication	Outcomes were assessed from 2012-2013 (approximately 2 years).	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).
Total Cancer Except Non-melanoma Skin Cancer	Outcomes were assessed from 1996-2020 (approximately 24 years).	All primary incident cancers except non-melanoma skin cancer
Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)	Outcomes were assessed from 1996-2025 (approximately 29 years).	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.

Secondary Outcome Measures

Name	Time	Method
Short Physical Performance Battery	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.	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.
Subclinical Atherosclerosis	Outcomes were assessed from 2012-2013 (approximately 2 years).	Measured using coronary artery calcification (CAC).
Cognitive Function	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.	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 ).
Frailty	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.	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.
Mortality	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.	All cause-mortality through clinic reports and National Death Index search