Diabetes MellitusPhase 3DPPOSNCT00038727

Diabetes Prevention Program Outcomes Study

A Phase 3 study testing DPPOS Group Lifestyle, Metformin and DPPOS Boost Lifestyle in people with Diabetes Mellitus and Cancer, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 25 years and older
Conditions the study is for: Diabetes Mellitus, Cancer, CVD
What is being tested?: DPPOS Group Lifestyle, Metformin and DPPOS Boost Lifestyle
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,779 participants
Where: 1 siteUnited States
Study dates: 31 Jul 1996to 30 Apr 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 years and older
All sexes
No healthy volunteers
Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

George Washington University
Rockville, Maryland, 20852

Other trials in United States

About this study

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.

Read the 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

Conditions: Diabetes Mellitus, Cancer, CVD
Being tested: DPPOS Group Lifestyle, Metformin, DPPOS Boost Lifestyle, Intensive Lifestyle Group Session
Keywords: DPP, IGT, Prediabetes, Type 2 diabetes, Macrovascular disease, Microvascular disease, Lifestyle, Metformin, Obesity
Medical subject headings: Diabetes Mellitus, Neoplasms, Prediabetic State, Diabetes Mellitus, Type 2, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DPPOS Group LifestyleBehavioural
Quarterly group lifestyle sessions
MetforminDrug
Also called Glucophage
Administered as 850mg twice per day, masked in DPP and open label in DPPOS
DPPOS Boost LifestyleBehavioural
In addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.
Intensive Lifestyle Group SessionBehavioural
Also called Intensive lifestyle session (ILS)
16 session curriculum in group format. In DPP delivered to ILS as individual sessions

Study groups in NCT00038727
Study group	Role	What they receive
1 Original Lifestyle	Active comparator	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 Receives: Behavioral: DPPOS Group Lifestyle; Behavioral: DPPOS Boost Lifestyle; Behavioral: Intensive Lifestyle Group Session
2 Original Metformin	Active comparator	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. Receives: Behavioral: DPPOS Group Lifestyle; Drug: Metformin; Behavioral: Intensive Lifestyle Group Session
3 Original Placebo	Placebo comparator	randomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2 Receives: Behavioral: DPPOS Group Lifestyle; Behavioral: Intensive Lifestyle Group Session

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Diabetes.
Primary outcome 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).
Measured: Outcomes were assessed from 1996-2020 for median follow-up of 21 years and a maximum follow-up of 23 years including a median of 3 years in DPP in all participants enrolled in DPPOS.
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).
Measured: Outcomes were assessed from 2012-2013 (approximately 2 years).
Number of Participants With Total Cancer Except Non-melanoma Skin Cancer
All primary cancers except non-melanoma skin cancer that occurred after randomization in DPP
Measured: Outcomes were assessed from 1996-2020 (approximately 24 years).
Number of Participants With Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)
MACE includes MI, stroke or CVD death that occurred after randomization and adjudicated by an outcomes committee who are blinded to treatment assignment.
Measured: Outcomes were assessed from 1996-2019 over a total median follow-up of 21 years since DPP randomization

Secondary outcomes (5)

Subclinical Atherosclerosis
Measured using coronary artery calcification (CAC).
Measured: Outcomes were assessed from 2012-2013 (approximately 2 years).
Cognitive Function
Cognitive function was defined by tests of memory SEVLT (Spanish English Verbal Learning Test) and executive function, DSST (Digit Symbol Substitution Test). The measure of memory was the Spanish English Verbal Learning Test (SEVLT). The SEVLT consists of recalling a list of 15 words in three trials of immediate recall and one trial after a distractor list. The total number of correct words recalled after four trials is the outcome reported.The test of frontal-executive abilities was the total score in the Digit Symbol Substitution Test (DSST). The DSST is a test in which participants try to match numbers to symbols in 90 s. The total number of correct answers is reported.
Measured: Outcomes were assessed in visit year 8 starting in 2010
Short Physical Performance Battery
Physical function is measured using the short physical performance battery (SPPB), which ranges from 0-12 and 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 and derived as SPPB= (balance score + gait score + chair score). Each sub scale is 0, 1, 2, 3 or 4 depending on the gender specific quintiles with 0 being the lowest and 4 being the highest functional status as described in Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994 Mar 1;49(2):M85-94.
Measured: Outcomes were assessed in visit years 8, 10 , and 15 which started in 2010, 2012, and 2017, respectively
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.
Measured: Outcomes were assessed in DPPOS Visits years 8, 10 and 15 which started in 2010, 2012, and 2017
Mortality
All cause-mortality through clinic reports and National Death Index search
Measured: Outcomes were assessed throughout follow-up from 1996 to 2019. National Death Index search conducted in 2019 using early release data as of Dec 2018.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 199630 Apr 2022

First posted5 Jun 2002 (estimated)
Study start31 Jul 1996
Primary completion28 Feb 2020
Study completion30 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (47)Papers the sponsor has linked to this study.
Other trials for Diabetes MellitusStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: The study metformin was discontinued in January 31st, 2021. The current protocol is limited to long-term follow-up and does not involve any investigational product assignment.
Masking: None (open label)
Enrolment: 2,779 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00038727
Sponsor's protocol ID: DPPOS
Other IDs: U01DK048489
Acronym: DPPOS
Status last verified: Jul 2026
First submitted: 4 Jun 2002
Last updated: 30 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository

Publications

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
PubMed 11832527
Diabetes Prevention Program Research Group; Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009 Nov 14;374(9702):1677-86. doi: 10.1016/S0140-6736(09)61457-4. Epub 2009 Oct 29.
PubMed 19878986
Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015 Nov;3(11):866-75. doi: 10.1016/S2213-8587(15)00291-0. Epub 2015 Sep 13.
PubMed 26377054
Salive ME, Tjaden AH, Ames JR, Crandall JP, Dabelea D, Hazuda HP, Heckman-Stoddard BM, Huckfeldt PJ, Kuo S, Strotmeyer ES, Temprosa M, Venditti EM; DPP Research Group. Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes. JAMA. 2026 Jun 15:e268492. doi: 10.1001/jama.2026.8492. Online ahead of print.
PubMed 42295772
Lin PD, Cardenas A, Temprosa M, Botelho JC, Calafat AM, Gold DR, Oken E, Fleisch AF. Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program. J Am Heart Assoc. 2026 Jan 6;15(1):e046298. doi: 10.1161/JAHA.125.046298. Epub 2025 Dec 18.
PubMed 41413398
Tjaden AH, Goldbaum AA, Edelstein SL, Heckman-Stoddard BM, Reedy J, Herman WH, Hoskin M, Knowler WC, Schlogl M, Temple KA, Venditti EM, Watson K, Temprosa M, Shams-White MM; DPP Research Group. The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and Cancer Risk: results from the diabetes prevention program outcomes study. Am J Clin Nutr. 2025 Sep;122(3):715-723. doi: 10.1016/j.ajcnut.2025.07.011. Epub 2025 Jul 15.
PubMed 40675492
Knowler WC, Doherty L, Edelstein SL, Bennett PH, Dabelea D, Hoskin M, Kahn SE, Kalyani RR, Kim C, Pi-Sunyer FX, Raghavan S, Shah VO, Temprosa M, Venditti EM, Nathan DM; DPP/DPPOS Research Group. Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):469-481. doi: 10.1016/S2213-8587(25)00022-1. Epub 2025 Apr 28.
PubMed 40311647
Munshi MN, Venditti EM, Tjaden AH, Knowler WC, Boyko EJ, Middelbeek RJW, Luchsinger JA, Lee CG, Hazuda HP, Salive ME, Edelstein SL, Storer TW. Long-term impact of Diabetes Prevention Program interventions on walking endurance. Front Public Health. 2024 Dec 18;12:1470035. doi: 10.3389/fpubh.2024.1470035. eCollection 2024.
PubMed 39744353
Gadde KM, Yin X, Goldberg RB, Orchard TJ, Schlogl M, Dabelea D, Ibebuogu UN, Watson KE, Pi-Sunyer FX, Crandall JP, Temprosa M, Luchsinger JA; Diabetes Prevention Program Research Group. Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study. J Am Heart Assoc. 2023 Nov 7;12(21):e029671. doi: 10.1161/JAHA.123.029671. Epub 2023 Nov 6.
PubMed 37929764
Molitch ME, Tripputi M, Levey AS, Crandall JP, Dabelea D, Herman WH, Knowler WC, Orchard TJ, Schroeder EB, Srikanthan P, Temprosa M, White NH, Nathan DM; Diabetes Prevention Program Research Group. Electronic address: dppmail@bsc.gwu.edu. Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS. J Diabetes Complications. 2023 Sep;37(9):108556. doi: 10.1016/j.jdiacomp.2023.108556. Epub 2023 Jul 25.
PubMed 37607422
Shams-White MM, Tjaden AH, Edelstein SL, Bassiouni S, Kahle LL, Kim C, Pi-Sunyer X, Temple KA, Venditti EM, Reedy J, Heckman-Stoddard BM; DPP Research Group. The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) score and diabetes risk in the Diabetes Prevention Program Outcomes Study (DPPOS). BMC Nutr. 2022 Sep 21;8(1):105. doi: 10.1186/s40795-022-00596-7.
PubMed 36131333
Goldberg RB, Orchard TJ, Crandall JP, Boyko EJ, Budoff M, Dabelea D, Gadde KM, Knowler WC, Lee CG, Nathan DM, Watson K, Temprosa M; Diabetes Prevention Program Research Group*. Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study. Circulation. 2022 May 31;145(22):1632-1641. doi: 10.1161/CIRCULATIONAHA.121.056756. Epub 2022 May 23.
PubMed 35603600
Lee CG, Heckman-Stoddard B, Dabelea D, Gadde KM, Ehrmann D, Ford L, Prorok P, Boyko EJ, Pi-Sunyer X, Wallia A, Knowler WC, Crandall JP, Temprosa M; Diabetes Prevention Program Research Group; Diabetes Prevention Program Research Group:. Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2021 Dec;44(12):2775-2782. doi: 10.2337/dc21-1046. Epub 2021 Oct 25.
PubMed 34697033
Varga TV, Liu J, Goldberg RB, Chen G, Dagogo-Jack S, Lorenzo C, Mather KJ, Pi-Sunyer X, Brunak S, Temprosa M; Diabetes Prevention Program Research Group. Predictive utilities of lipid traits, lipoprotein subfractions and other risk factors for incident diabetes: a machine learning approach in the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2021 Mar;9(1):e001953. doi: 10.1136/bmjdrc-2020-001953.
PubMed 33789908
Kriska AM, Rockette-Wagner B, Edelstein SL, Bray GA, Delahanty LM, Hoskin MA, Horton ES, Venditti EM, Knowler WC; DPP Research Group. The Impact of Physical Activity on the Prevention of Type 2 Diabetes: Evidence and Lessons Learned From the Diabetes Prevention Program, a Long-Standing Clinical Trial Incorporating Subjective and Objective Activity Measures. Diabetes Care. 2021 Jan;44(1):43-49. doi: 10.2337/dc20-1129. Epub 2020 Nov 10.
PubMed 33444158

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Diabetes Prevention Program Outcomes Study
ClinicalTrials.gov ID: NCT00038727
Acronym / sponsor ID: DPPOS / DPPOS
Conditions: Diabetes Mellitus, Cancer, CVD
Keywords: DPP, IGT, Prediabetes, Type 2 diabetes, Macrovascular disease, Microvascular disease, Lifestyle, Metformin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,779 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Collaborators: 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 (IHS), General Clinical Research Program, US Department of Veterans Affairs
Study start: 31 Jul 1996 (actual)
Primary completion: 28 Feb 2020 (actual)
Study completion: 30 Apr 2022 (actual)
First posted: 5 Jun 2002 (estimated)
Results: Posted 24 Oct 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: The study metformin was discontinued in January 31st, 2021. The current protocol is limited to long-term follow-up and does not involve any investigational product assignment.

Arm	Type	Receives
1 Original Lifestyle	Active comparator	Behavioral: DPPOS Group Lifestyle, Behavioral: DPPOS Boost Lifestyle, Behavioral: Intensive Lifestyle Group Sessionrandomized 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	Active comparator	Behavioral: DPPOS Group Lifestyle, Drug: Metformin, Behavioral: Intensive Lifestyle Group Sessionrandomized 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	Placebo comparator	Behavioral: DPPOS Group Lifestyle, Behavioral: Intensive Lifestyle Group Sessionrandomized to masked placebo during DPP and offered Intensive Lifestyle Group Session, DPPOS Group Lifestyle in DPPOS Phase 1 and 2

Who may qualify

Ages: 25 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DPPOS Group LifestyleQuarterly group lifestyle sessions	Behavioural	1 Original Lifestyle, 2 Original Metformin, 3 Original Placebo
MetforminAlso: GlucophageAdministered as 850mg twice per day, masked in DPP and open label in DPPOS	Drug	2 Original Metformin
DPPOS Boost LifestyleIn addition to quarterly group, 2 additional classes per year and an annual 15 minute check-up.	Behavioural	1 Original Lifestyle
Intensive Lifestyle Group SessionAlso: Intensive lifestyle session (ILS)16 session curriculum in group format. In DPP delivered to ILS as individual sessions	Behavioural	1 Original Lifestyle, 2 Original Metformin, 3 Original Placebo

Primary outcome

Number of Participants With Diabetes.
Time frame: Outcomes were assessed from 1996-2020 for median follow-up of 21 years and a maximum follow-up of 23 years including a median of 3 years in DPP in all participants enrolled in DPPOS.
Primary outcome 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
Time frame: 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).
Number of Participants With Total Cancer Except Non-melanoma Skin Cancer
Time frame: Outcomes were assessed from 1996-2020 (approximately 24 years).
All primary cancers except non-melanoma skin cancer that occurred after randomization in DPP
Number of Participants With Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)
Time frame: Outcomes were assessed from 1996-2019 over a total median follow-up of 21 years since DPP randomization
MACE includes MI, stroke or CVD death that occurred after randomization and adjudicated by an outcomes committee who are blinded to treatment assignment.

5 secondary outcomes

Subclinical Atherosclerosis
Time frame: Outcomes were assessed from 2012-2013 (approximately 2 years).
Cognitive Function
Time frame: Outcomes were assessed in visit year 8 starting in 2010
Short Physical Performance Battery
Time frame: Outcomes were assessed in visit years 8, 10 , and 15 which started in 2010, 2012, and 2017, respectively
Frailty
Time frame: Outcomes were assessed in DPPOS Visits years 8, 10 and 15 which started in 2010, 2012, and 2017
Mortality
Time frame: Outcomes were assessed throughout follow-up from 1996 to 2019. National Death Index search conducted in 2019 using early release data as of Dec 2018.

Results and safety

Results posted to the registry on 24 Oct 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1A DPPOS Original Lifestyle	1,079	916
2A DPPOS Original Metformin	1,073	927
3A DPPOS Original Placebo	1,082	936

Primary outcome: Number of Participants With Diabetes.

Time frame: Outcomes were assessed from 1996-2020 for median follow-up of 21 years and a maximum follow-up of 23 years including a median of 3 years in DPP in all participants enrolled in DPPOS.. Count of participants. Unit: Participants

Measure	1 Original Lifestyle n = 916	2 Original Metformin n = 927	3 Original Placebo n = 936
Value	554	565	624

Population analysed: Participants enrolled in DPPOS with evaluable diabetes outcome data during follow-up were included in the analysis (N=916, 927, and 936 for the lifestyle, metformin, and placebo groups, respectively).

Primary outcome: Prevalence of Aggregate Microvascular Complication

Time frame: Outcomes were assessed from 2012-2013 (approximately 2 years).. Number (95% Confidence Interval). Unit: average percentage of participants

Measure	1 Original Lifestyle n = 751	2 Original Metformin n = 772	3 Original Placebo n = 780
Value	11.3 (10.1 to 12.7)	13 (11.7 to 14.5)	12.4 (11.1 to 13.8)

Population analysed: Number with microvascular outcome data and included in the primary outcome analysis

Primary outcome: Number of Participants With Total Cancer Except Non-melanoma Skin Cancer

Time frame: Outcomes were assessed from 1996-2020 (approximately 24 years).. Count of participants. Unit: Participants

Measure	1 Original Lifestyle n = 1074	2 Original Metformin n = 1068	3 Original Placebo n = 1073
Value	182	173	191

Population analysed: DPPOS is the long-term follow-up of the 3234 participants randomized in the Diabetes Prevention Program with ClinicalTrials.gov Identifier: NCT00004992. All surviving DPP participants were invited to enroll into DPPOS and 2779 consented. All participants randomized to DPP were included in this analysis including those who did not enroll in DPPOS except those who did not have follow-up after DPP randomization (5 lifestyle, 5 metformin, 9 placebo) since records were not collected.

Primary outcome: Number of Participants With Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)

Time frame: Outcomes were assessed from 1996-2019 over a total median follow-up of 21 years since DPP randomization. Count of participants. Unit: Participants

Measure	1 Original Lifestyle n = 1079	2 Original Metformin n = 1073	3 Original Placebo n = 1082
Value	111	101	98

Population analysed: DPPOS is the long-term follow-up of the 3234 participants randomized in the Diabetes Prevention Program with ClinicalTrials.gov Identifier: NCT00004992. All surviving DPP participants were invited to enroll into DPPOS and 2779 agreed to be part of DPPOS. All participants randomized to DPP were included in this analysis including those who did not enroll in DPPOS for the period of time they contributed data.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: DPPOS began in 2002 and by the data lock in February 2020, had a median follow-up of 21 years since the initial randomization in DPP. DPP spanned from 1996-1999 for 2.7 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1 Original Lifestyle Enrolled in DPPOS	649 of 916 (70.9%)	302 of 916 (33%)	129 of 916
2 Original Metformin Enrolled in DPPOS	657 of 927 (70.9%)	347 of 927 (37.4%)	122 of 927
3 Original Placebo Enrolled in DPPOS	646 of 936 (69%)	338 of 936 (36.1%)	143 of 936
1B Randomized Lifestyle During DPP	235 of 1,079 (21.8%)	0 of 0	158 of 1,079
2B Randomized Metformin During DPP	251 of 1,073 (23.4%)	0 of 0	152 of 1,073
3B Randomized Placebo During DPP	238 of 1,082 (22%)	0 of 0	143 of 1,082

Limitations and caveats (from the sponsor): Not all participants randomized in the original Diabetes Prevention Program (DPP) enrolled in the DPPOS follow-up study. Outcome ascertainment and adverse event collection procedures differed between the original DPP and DPPOS follow-up phases. Some assessments were conducted only in subsets of participants who completed specific evaluations during follow-up.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 11832527Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
Results publication: PubMed 19878986Diabetes Prevention Program Research Group; Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009 Nov 14;374(9702):1677-86. doi: 10.1016/S0140-6736(09)61457-4. Epub 2009 Oct 29.
Results publication: PubMed 26377054Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015 Nov;3(11):866-75. doi: 10.1016/S2213-8587(15)00291-0. Epub 2015 Sep 13.
Derived from this study: PubMed 42295772Salive ME, Tjaden AH, Ames JR, Crandall JP, Dabelea D, Hazuda HP, Heckman-Stoddard BM, Huckfeldt PJ, Kuo S, Strotmeyer ES, Temprosa M, Venditti EM; DPP Research Group. Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes. JAMA. 2026 Jun 15:e268492. doi: 10.1001/jama.2026.8492. Online ahead of print.
Derived from this study: PubMed 41413398Lin PD, Cardenas A, Temprosa M, Botelho JC, Calafat AM, Gold DR, Oken E, Fleisch AF. Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program. J Am Heart Assoc. 2026 Jan 6;15(1):e046298. doi: 10.1161/JAHA.125.046298. Epub 2025 Dec 18.
Derived from this study: PubMed 40675492Tjaden AH, Goldbaum AA, Edelstein SL, Heckman-Stoddard BM, Reedy J, Herman WH, Hoskin M, Knowler WC, Schlogl M, Temple KA, Venditti EM, Watson K, Temprosa M, Shams-White MM; DPP Research Group. The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and Cancer Risk: results from the diabetes prevention program outcomes study. Am J Clin Nutr. 2025 Sep;122(3):715-723. doi: 10.1016/j.ajcnut.2025.07.011. Epub 2025 Jul 15.
Derived from this study: PubMed 40311647Knowler WC, Doherty L, Edelstein SL, Bennett PH, Dabelea D, Hoskin M, Kahn SE, Kalyani RR, Kim C, Pi-Sunyer FX, Raghavan S, Shah VO, Temprosa M, Venditti EM, Nathan DM; DPP/DPPOS Research Group. Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial. Lancet Diabetes Endocrinol. 2025 Jun;13(6):469-481. doi: 10.1016/S2213-8587(25)00022-1. Epub 2025 Apr 28.
Derived from this study: PubMed 39744353Munshi MN, Venditti EM, Tjaden AH, Knowler WC, Boyko EJ, Middelbeek RJW, Luchsinger JA, Lee CG, Hazuda HP, Salive ME, Edelstein SL, Storer TW. Long-term impact of Diabetes Prevention Program interventions on walking endurance. Front Public Health. 2024 Dec 18;12:1470035. doi: 10.3389/fpubh.2024.1470035. eCollection 2024.
Derived from this study: PubMed 37929764Gadde KM, Yin X, Goldberg RB, Orchard TJ, Schlogl M, Dabelea D, Ibebuogu UN, Watson KE, Pi-Sunyer FX, Crandall JP, Temprosa M, Luchsinger JA; Diabetes Prevention Program Research Group. Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study. J Am Heart Assoc. 2023 Nov 7;12(21):e029671. doi: 10.1161/JAHA.123.029671. Epub 2023 Nov 6.
Derived from this study: PubMed 37607422Molitch ME, Tripputi M, Levey AS, Crandall JP, Dabelea D, Herman WH, Knowler WC, Orchard TJ, Schroeder EB, Srikanthan P, Temprosa M, White NH, Nathan DM; Diabetes Prevention Program Research Group. Electronic address: dppmail@bsc.gwu.edu. Effects of metformin and intensive lifestyle interventions on the incidence of kidney disease in adults in the DPP/DPPOS. J Diabetes Complications. 2023 Sep;37(9):108556. doi: 10.1016/j.jdiacomp.2023.108556. Epub 2023 Jul 25.
Derived from this study: PubMed 36131333Shams-White MM, Tjaden AH, Edelstein SL, Bassiouni S, Kahle LL, Kim C, Pi-Sunyer X, Temple KA, Venditti EM, Reedy J, Heckman-Stoddard BM; DPP Research Group. The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) score and diabetes risk in the Diabetes Prevention Program Outcomes Study (DPPOS). BMC Nutr. 2022 Sep 21;8(1):105. doi: 10.1186/s40795-022-00596-7.
Derived from this study: PubMed 35603600Goldberg RB, Orchard TJ, Crandall JP, Boyko EJ, Budoff M, Dabelea D, Gadde KM, Knowler WC, Lee CG, Nathan DM, Watson K, Temprosa M; Diabetes Prevention Program Research Group*. Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study. Circulation. 2022 May 31;145(22):1632-1641. doi: 10.1161/CIRCULATIONAHA.121.056756. Epub 2022 May 23.
Study websiteLink provided by the sponsor.
Clinical trials.gov entry for DPPLink provided by the sponsor.
Individual participant dataSharing planned: Yes. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David M. Nathan, MD study chair

Massachusetts General Hospital

Marinella Temprosa, PhD principal investigator

George Washington University Biostatistics Center

Barbara Linder, MD, PhD study director

NIDDK Project Scientist

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Diabetes. (time frame: Outcomes were assessed from 1996-2020 for median follow-up of 21 years and a maximum follow-up of 23 years including a median of 3 years in DPP in all participants enrolled in DPPOS.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00038727, which also lists 47 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.