Diabetes Prevention Program Outcomes Study (DPPOS)

• ClinicalTrials.gov Identifier: NCT00038727
• Recruitment Status: Active, not recruiting
• First Posted: June 5, 2002
• Results First Posted: October 24, 2017
• Last Update Posted: December 28, 2021
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• 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; General Clinical Research Program; US Department of Veterans Affairs
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Diabetes Mellitus; Cancer; CVD
• Interventions: Behavioral: DPPOS Group Lifestyle; Drug: Metformin; Behavioral: DPPOS Boost Lifestyle; Behavioral: Intensive Lifestyle Group Session
• Enrollment: 2779

Participant Flow

Recruitment Details	All surviving Diabetes Prevention Program (DPP) participants with consent were invited to enroll into DPPOS throughout the follow-up period. The majority of DPPOS participants were enrolled in 2002-2003.
Pre-assignment Details	DPPOS covers 3 funding phases for the 3 study phases: DPPOS-1 (2002-2008), DPPOS-2 (2009-2014), DPPOS-3 (2015-2021). The groups are defined using the original randomized groups from DPP with recruitment period of 1996-1998.

Arm/Group Title	1 Original Lifestyle	2 Original Metformin	3 Original Placebo
Arm/Group Description	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.	Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day	Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Period Title: Overall Study
Started	916 [1]	927 [1]	936 [1]
DPPOS Phase 1 Primary	910 [2]	924 [2]	932 [2]
DPPOS Phase 2 Enrolled	915 [3]	926 [3]	935 [3]
DPPOS Phase 2 Primary	751 [3]	772 [3]	780 [3]
DPPOS Phase 3 Enrolled [4]	916	927	936
Completed	916	927	936
Not Completed	0	0	0
[1] Includes all enrollees from DPPOS 1-3; [2] As reported in the Lancet 2009; [3] As reported in Lancet Diabetes and Endocrinology 2015; [4] As of February 2016

Baseline Characteristics

Arm/Group Title		1 Original Lifestyle	2 Original Metformin	3 Original Placebo	Total
Arm/Group Description		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 of all reporting groups
Overall Number of Baseline Participants		916	927	936	2779
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	915 participants	927 participants	936 participants	2778 participants
		54 (11)	54 (10)	54 (10)	54 (10)
		[1] Measure Analysis Population Description: An additional 3 participants were enrolled after publication
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	916 participants	927 participants	936 participants	2779 participants
		51.2 (11.1)	51.3 (10.1)	50.7 (10.0)	51.1 (10.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	916 participants	927 participants	936 participants	2779 participants
	Female	624 68.1%	620 66.9%	645 68.9%	1889 68.0%
	Male	292 31.9%	307 33.1%	291 31.1%	890 32.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	916 participants	927 participants	936 participants	2779 participants
	American Indian or Alaska Native	54 5.9%	46 5.0%	55 5.9%	155 5.6%
	Asian	44 4.8%	28 3.0%	40 4.3%	112 4.0%
	Native Hawaiian or Other Pacific Islander	8 0.9%	1 0.1%	1 0.1%	10 0.4%
	Black or African American	173 18.9%	182 19.6%	189 20.2%	544 19.6%
	White	596 65.1%	628 67.7%	612 65.4%	1836 66.1%
	More than one race	19 2.1%	21 2.3%	19 2.0%	59 2.1%
	Unknown or Not Reported	22 2.4%	21 2.3%	20 2.1%	63 2.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	916 participants	927 participants	936 participants	2779 participants
		916	927	936	2779
BMI; Mean (Standard Deviation); Unit of measure: Kg/m2
	Number Analyzed	916 participants	927 participants	936 participants	2779 participants
		33.7 (6.5)	33.8 (6.5)	34.0 (6.5)	33.8 (6.5)

Outcome Measures

1. Primary Outcome

Title	Development of Diabetes.
Description	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).
Time Frame	Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Original Lifestyle	2 Original Metformin	3 Original Placebo
Arm/Group Description:	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.	Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day	Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Overall Number of Participants Analyzed	916	927	936
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: diabetes incidence (cases per 100 person
	5.3; (4.8 to 5.8)	6.4; (5.9 to 7.1)	7.8; (7.2 to 8.6)

2. Primary Outcome

Title	Prevalence of Aggregate Microvascular Complication
Description	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).
Time Frame	Outcomes were assessed from 2012-2013 (approximately 2 years).

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	1 Original Lifestyle	2 Original Metformin	3 Original Placebo
Arm/Group Description:	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.	Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day	Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Overall Number of Participants Analyzed	751	772	780
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: average percentage of participants
	11.3; (10.1 to 12.7)	13; (11.7 to 14.5)	12.4; (11.1 to 13.8)

3. Primary Outcome

Title	Total Cancer Except Non-melanoma Skin Cancer
Description	All primary incident cancers except non-melanoma skin cancer
Time Frame	Outcomes were assessed from 1996-2020 (approximately 24 years).

Outcome Measure Data Not Reported

4. Primary Outcome

Title	Major Adverse Cardiovascular Events (MACE): Myocardial Infarction (MI), Stroke, or Cardiovascular Death (CVD)
Description	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.
Time Frame	Outcomes were assessed from 1996-2025 (approximately 29 years).

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Subclinical Atherosclerosis
Description	Measured using coronary artery calcification (CAC).
Time Frame	Outcomes were assessed from 2012-2013 (approximately 2 years).

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		1 Original Lifestyle	2 Original Metformin	3 Original Placebo
Arm/Group Description:		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	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
Overall Number of Participants Analyzed		701	679	681
Geometric Mean (95% Confidence Interval); Unit of Measure: CAC geometric mean in AU
Men	Number Analyzed	468 participants	464 participants	486 participants
		70.1; (45.4 to 108.2)	40.2; (26.1 to 61.9)	63.7; (41.3 to 98.3)
Women	Number Analyzed	213 participants	215 participants	215 participants
		6.0; (4.1 to 8.8)	6.1; (4.2 to 9.0)	5.3; (3.6 to 7.8)

6. Secondary Outcome

Title	Cognitive Function
Description	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 ).
Time Frame	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Short Physical Performance Battery
Description	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.
Time Frame	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Frailty
Description	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.
Time Frame	Outcomes were assessed in visit years starting in 2010, 2012, 2017, 2020.

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	Mortality
Description	All cause-mortality through clinic reports and National Death Index search
Time Frame	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.

Outcome Measure Data

Analysis Population Description

All randomized to DPP were included

Arm/Group Title	1 Original Lifestyle	2 Original Metformin	3 Original Placebo
Arm/Group Description:	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.	Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day	Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Overall Number of Participants Analyzed	1079	1073	1082
Measure Type: Count of Participants; Unit of Measure: Participants
	158 14.6%	152 14.2%	143 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1 Original Lifestyle, 3 Original Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.87
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.28
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2 Original Metformin, 3 Original Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.95
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.25
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Until data lock of Jan 2014, average of 15 years of follow-up
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	1 Original Lifestyle		2 Original Metformin		3 Original Placebo
Arm/Group Description	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.		Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day		Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
All-Cause Mortality
	1 Original Lifestyle		2 Original Metformin		3 Original Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	88/916 (9.61%)		85/927 (9.17%)		83/936 (8.87%)
Serious Adverse Events
	1 Original Lifestyle		2 Original Metformin		3 Original Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	472/916 (51.53%)		482/927 (52.00%)		492/936 (52.56%)
General disorders
Any SAE Report † 1	472/916 (51.53%)	1099	482/927 (52.00%)	1122	492/936 (52.56%)	1103
1 Term from vocabulary, Costart dictionary; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	1 Original Lifestyle		2 Original Metformin		3 Original Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	234/916 (25.55%)		274/927 (29.56%)		257/936 (27.46%)
Musculoskeletal and connective tissue disorders
Sprains and fractures requiring medical attention † 1	234/916 (25.55%)		274/927 (29.56%)		257/936 (27.46%)
1 Term from vocabulary, Costart dictionary; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Marinella Temprosa, PI of Coordinating Center
• Organization: George Washington University
• Phone: 3018819260
• EMail: ella@bsc.gwu.edu

Publications of Results:

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. Erratum In: Lancet. 2009 Dec 19;374(9707):2054.

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.

Other 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

Hazuda HP, Pan Q, Florez H, Luchsinger JA, Crandall JP, Venditti EM, Golden SH, Kriska AM, Bray GA. Association of Intensive Lifestyle and Metformin Interventions With Frailty in the Diabetes Prevention Program Outcomes Study. J Gerontol A Biol Sci Med Sci. 2021 Apr 30;76(5):929-936. doi: 10.1093/gerona/glaa295.

Kim C, Younes N, Temprosa M, Edelstein S, Goldberg RB, Araneta MG, Wallia A, Brown A, Darwin C, Ibebuogu U, Pi-Sunyer X, Knowler WC. Infertility, Gravidity, and Risk Of Diabetes among High-Risk Women in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e358-67. doi: 10.1210/clinem/dgaa013.

Perreault L, Pan Q, Schroeder EB, Kalyani RR, Bray GA, Dagogo-Jack S, White NH, Goldberg RB, Kahn SE, Knowler WC, Mathioudakis N, Dabelea D; Diabetes Prevention Program Research Group. Regression From Prediabetes to Normal Glucose Regulation and Prevalence of Microvascular Disease in the Diabetes Prevention Program Outcomes Study (DPPOS). Diabetes Care. 2019 Sep;42(9):1809-1815. doi: 10.2337/dc19-0244. Epub 2019 Jul 18.

Cardenas A, Hivert MF, Gold DR, Hauser R, Kleinman KP, Lin PD, Fleisch AF, Calafat AM, Ye X, Webster TF, Horton ES, Oken E. Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Incident Diabetes and Microvascular Disease. Diabetes Care. 2019 Sep;42(9):1824-1832. doi: 10.2337/dc18-2254. Epub 2019 Jul 11.

Apolzan JW, Venditti EM, Edelstein SL, Knowler WC, Dabelea D, Boyko EJ, Pi-Sunyer X, Kalyani RR, Franks PW, Srikanthan P, Gadde KM; Diabetes Prevention Program Research Group. Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study. Ann Intern Med. 2019 May 21;170(10):682-690. doi: 10.7326/M18-1605. Epub 2019 Apr 23. Erratum In: Ann Intern Med. 2020 Sep 15;173(6):508.

Diabetes Prevention Program Research Group. Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2019 Apr;42(4):601-608. doi: 10.2337/dc18-1970.

Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Fleisch AF, Lin PD, Calafat AM, Webster TF, Horton ES, Oken E. Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity. JAMA Netw Open. 2018 Aug 3;1(4):e181493. doi: 10.1001/jamanetworkopen.2018.1493.

Kim C, Ricardo AC, Boyko EJ, Christophi CA, Temprosa M, Watson KE, Pi-Sunyer X, Kalyani RR; Diabetes Prevention Program Research Group. Sex Hormones and Measures of Kidney Function in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1171-1180. doi: 10.1210/jc.2018-01495.

DeBoer MD, Filipp SL, Gurka MJ. Use of a Metabolic Syndrome Severity Z Score to Track Risk During Treatment of Prediabetes: An Analysis of the Diabetes Prevention Program. Diabetes Care. 2018 Nov;41(11):2421-2430. doi: 10.2337/dc18-1079. Epub 2018 Oct 1.

Kim C, Aroda VR, Goldberg RB, Younes N, Edelstein SL, Carrion-Petersen M, Ehrmann DA; Diabetes Prevention Program Outcomes Study Group. Androgens, Irregular Menses, and Risk of Diabetes and Coronary Artery Calcification in the Diabetes Prevention Program. J Clin Endocrinol Metab. 2018 Feb 1;103(2):486-496. doi: 10.1210/jc.2017-01829.

Crandall JP, Mather K, Rajpathak SN, Goldberg RB, Watson K, Foo S, Ratner R, Barrett-Connor E, Temprosa M. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care. 2017 Oct 10;5(1):e000438. doi: 10.1136/bmjdrc-2017-000438. eCollection 2017. Erratum In: BMJ Open Diabetes Res Care. 2017 Oct 25;5(1):e000438corr1.

Perreault L, Pan Q, Aroda VR, Barrett-Connor E, Dabelea D, Dagogo-Jack S, Hamman RF, Kahn SE, Mather KJ, Knowler WC; Diabetes Prevention Program Research Group. Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS). Diabet Med. 2017 Dec;34(12):1747-1755. doi: 10.1111/dme.13453. Epub 2017 Sep 19.

Aroda VR, Knowler WC, Crandall JP, Perreault L, Edelstein SL, Jeffries SL, Molitch ME, Pi-Sunyer X, Darwin C, Heckman-Stoddard BM, Temprosa M, Kahn SE, Nathan DM; Diabetes Prevention Program Research Group. Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia. 2017 Sep;60(9):1601-1611. doi: 10.1007/s00125-017-4361-9. Epub 2017 Aug 2.

Kim C, Dabelea D, Kalyani RR, Christophi CA, Bray GA, Pi-Sunyer X, Darwin CH, Yalamanchi S, Barrett-Connor E, Golden SH, Boyko EJ. Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3381-3389. doi: 10.1210/jc.2017-00967.

Luchsinger JA, Ma Y, Christophi CA, Florez H, Golden SH, Hazuda H, Crandall J, Venditti E, Watson K, Jeffries S, Manly JJ, Pi-Sunyer FX; Diabetes Prevention Program Research Group. Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2017 Jul;40(7):958-965. doi: 10.2337/dc16-2376. Epub 2017 May 12.

Goldberg RB, Aroda VR, Bluemke DA, Barrett-Connor E, Budoff M, Crandall JP, Dabelea D, Horton ES, Mather KJ, Orchard TJ, Schade D, Watson K, Temprosa M; Diabetes Prevention Program Research Group. Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and Its Outcome Study on Coronary Artery Calcium. Circulation. 2017 Jul 4;136(1):52-64. doi: 10.1161/CIRCULATIONAHA.116.025483. Epub 2017 May 5.

Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, Crandall JP; Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr;101(4):1754-61. doi: 10.1210/jc.2015-3754. Epub 2016 Feb 22.

Herman WH. The cost-effectiveness of diabetes prevention: results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study. Clin Diabetes Endocrinol. 2015 Sep 2;1:9. doi: 10.1186/s40842-015-0009-1. eCollection 2015.

Marrero DG, Ma Y, de Groot M, Horton ES, Price DW, Barrett-Connor E, Carnethon MR, Knowler WC; Diabetes Prevention Program Research Group. Depressive symptoms, antidepressant medication use, and new onset of diabetes in participants of the diabetes prevention program and the diabetes prevention program outcomes study. Psychosom Med. 2015 Apr;77(3):303-10. doi: 10.1097/PSY.0000000000000156.

Aroda VR, Christophi CA, Edelstein SL, Zhang P, Herman WH, Barrett-Connor E, Delahanty LM, Montez MG, Ackermann RT, Zhuo X, Knowler WC, Ratner RE; Diabetes Prevention Program Research Group. The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up. J Clin Endocrinol Metab. 2015 Apr;100(4):1646-53. doi: 10.1210/jc.2014-3761. Epub 2015 Feb 23.

Diabetes Prevention Program Research Group. HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: a randomized clinical trial. Diabetes Care. 2015 Jan;38(1):51-8. doi: 10.2337/dc14-0886. Epub 2014 Oct 21.

Diabetes Prevention Program (DPP) Research Group; Hamman RF, Horton E, Barrett-Connor E, Bray GA, Christophi CA, Crandall J, Florez JC, Fowler S, Goldberg R, Kahn SE, Knowler WC, Lachin JM, Murphy MB, Venditti E. Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS). Diabetes. 2015 Mar;64(3):989-98. doi: 10.2337/db14-0333. Epub 2014 Oct 2.

Dabelea D, Ma Y, Knowler WC, Marcovina S, Saudek CD, Arakaki R, White NH, Kahn SE, Orchard TJ, Goldberg R, Palmer J, Hamman RF; Diabetes Prevention Program Research Group. Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program. Diabet Med. 2014 Sep;31(9):1064-8. doi: 10.1111/dme.12437. Epub 2014 Apr 9.

Marrero D, Pan Q, Barrett-Connor E, de Groot M, Zhang P, Percy C, Florez H, Ackermann R, Montez M, Rubin RR; DPPOS Research Group. Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study. Qual Life Res. 2014 Feb;23(1):75-88. doi: 10.1007/s11136-013-0436-3. Epub 2013 May 26.

Price DW, Ma Y, Rubin RR, Perreault L, Bray GA, Marrero D, Knowler WC, Barrett-Connor E, Lacoursiere DY; Diabetes Prevention Program Research Group. Depression as a predictor of weight regain among successful weight losers in the diabetes prevention program. Diabetes Care. 2013 Feb;36(2):216-21. doi: 10.2337/dc12-0293. Epub 2012 Sep 21.

Diabetes Prevention Program Outcomes Study Research Group; Orchard TJ, Temprosa M, Barrett-Connor E, Fowler SE, Goldberg RB, Mather KJ, Marcovina SM, Montez M, Ratner RE, Saudek CD, Sherif H, Watson KE. Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study. Diabet Med. 2013 Jan;30(1):46-55. doi: 10.1111/j.1464-5491.2012.03750.x.

Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE; Diabetes Prevention Program Research Group. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet. 2012 Jun 16;379(9833):2243-51. doi: 10.1016/S0140-6736(12)60525-X. Epub 2012 Jun 9.

Mather KJ, Christophi CA, Jablonski KA, Knowler WC, Goldberg RB, Kahn SE, Spector T, Dastani Z, Waterworth D, Richards JB, Funahashi T, Pi-Sunyer FX, Pollin TI, Florez JC, Franks PW; Diabetes Prevention Program Research Group. Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program. Diabet Med. 2012 Dec;29(12):1579-88. doi: 10.1111/j.1464-5491.2012.03662.x.

Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012 Apr;35(4):731-7. doi: 10.2337/dc11-1299.

Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care. 2012 Apr;35(4):723-30. doi: 10.2337/dc11-1468. Erratum In: Diabetes Care. 2013 Dec;36(12):4173-5.

Rubin RR, Ma Y, Peyrot M, Marrero DG, Price DW, Barrett-Connor E, Knowler WC; Diabetes Prevention Program Research Group. Antidepressant medicine use and risk of developing diabetes during the diabetes prevention program and diabetes prevention program outcomes study. Diabetes Care. 2010 Dec;33(12):2549-51. doi: 10.2337/dc10-1033. Epub 2010 Aug 30.

Crandall JP, Polsky S, Howard AA, Perreault L, Bray GA, Barrett-Connor E, Brown-Friday J, Whittington T, Foo S, Ma Y, Edelstein SL; Diabetes Prevention Program Research Group. Alcohol consumption and diabetes risk in the Diabetes Prevention Program. Am J Clin Nutr. 2009 Sep;90(3):595-601. doi: 10.3945/ajcn.2008.27382. Epub 2009 Jul 29.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00038727
• Obsolete Identifiers: NCT00353314
• Other Study ID Numbers: DPPOS; U01DK048489 ( U.S. NIH Grant/Contract )
• First Submitted: June 4, 2002
• First Posted: June 5, 2002
• Results First Submitted: February 21, 2017
• Results First Posted: October 24, 2017
• Last Update Posted: December 28, 2021