Trial Outcomes & Findings for Diabetes Prevention Program Outcomes Study (NCT NCT00038727)

NCT ID: NCT00038727

Last Updated: 2021-12-28

Results Overview

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).

Recruitment status

UNKNOWN

Study phase

PHASE3

Target enrollment

2779 participants

Primary outcome timeframe

Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP).

Results posted on

2021-12-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
1 Original Lifestyle
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.
2 Original Metformin
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Overall Study
STARTED
916
927
936
Overall Study
DPPOS Phase 1 Primary
910
924
932
Overall Study
DPPOS Phase 2 Enrolled
915
926
935
Overall Study
DPPOS Phase 2 Primary
751
772
780
Overall Study
DPPOS Phase 3 Enrolled
916
927
936
Overall Study
COMPLETED
916
927
936
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An additional 3 participants were enrolled after publication

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
1 Original Lifestyle
n=916 Participants
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
2 Original Metformin
n=927 Participants
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
3 Original Placebo
n=936 Participants
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
n=2779 Participants
Total of all reporting groups
Age, Continuous
51.2 years
STANDARD_DEVIATION 11.1 • n=916 Participants
51.3 years
STANDARD_DEVIATION 10.1 • n=927 Participants
50.7 years
STANDARD_DEVIATION 10.0 • n=936 Participants
51.1 years
STANDARD_DEVIATION 10.4 • n=2779 Participants
Sex: Female, Male
Female
624 Participants
n=916 Participants
620 Participants
n=927 Participants
645 Participants
n=936 Participants
1889 Participants
n=2779 Participants
Sex: Female, Male
Male
292 Participants
n=916 Participants
307 Participants
n=927 Participants
291 Participants
n=936 Participants
890 Participants
n=2779 Participants
Race (NIH/OMB)
American Indian or Alaska Native
54 Participants
n=916 Participants
46 Participants
n=927 Participants
55 Participants
n=936 Participants
155 Participants
n=2779 Participants
Race (NIH/OMB)
Asian
44 Participants
n=916 Participants
28 Participants
n=927 Participants
40 Participants
n=936 Participants
112 Participants
n=2779 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
8 Participants
n=916 Participants
1 Participants
n=927 Participants
1 Participants
n=936 Participants
10 Participants
n=2779 Participants
Race (NIH/OMB)
Black or African American
173 Participants
n=916 Participants
182 Participants
n=927 Participants
189 Participants
n=936 Participants
544 Participants
n=2779 Participants
Race (NIH/OMB)
White
596 Participants
n=916 Participants
628 Participants
n=927 Participants
612 Participants
n=936 Participants
1836 Participants
n=2779 Participants
Race (NIH/OMB)
More than one race
19 Participants
n=916 Participants
21 Participants
n=927 Participants
19 Participants
n=936 Participants
59 Participants
n=2779 Participants
Race (NIH/OMB)
Unknown or Not Reported
22 Participants
n=916 Participants
21 Participants
n=927 Participants
20 Participants
n=936 Participants
63 Participants
n=2779 Participants
Region of Enrollment
United States
916 participants
n=916 Participants
927 participants
n=927 Participants
936 participants
n=936 Participants
2779 participants
n=2779 Participants
BMI
33.7 kg/m2
STANDARD_DEVIATION 6.5 • n=916 Participants
33.8 kg/m2
STANDARD_DEVIATION 6.5 • n=927 Participants
34.0 kg/m2
STANDARD_DEVIATION 6.5 • n=936 Participants
33.8 kg/m2
STANDARD_DEVIATION 6.5 • n=2779 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
1 Original Lifestyle
n=916 Participants
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.
2 Original Metformin
n=927 Participants
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=936 Participants
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Development of Diabetes.
5.3 diabetes incidence (cases per 100 person
Interval 4.8 to 5.8
6.4 diabetes incidence (cases per 100 person
Interval 5.9 to 7.1
7.8 diabetes incidence (cases per 100 person
Interval 7.2 to 8.6

PRIMARY outcome

Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

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

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).

Outcome measures

Outcome measures
Measure
1 Original Lifestyle
n=751 Participants
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.
2 Original Metformin
n=772 Participants
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=780 Participants
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Prevalence of Aggregate Microvascular Complication
11.3 average percentage of participants
Interval 10.1 to 12.7
13 average percentage of participants
Interval 11.7 to 14.5
12.4 average percentage of participants
Interval 11.1 to 13.8

PRIMARY outcome

Timeframe: Outcomes were assessed from 1996-2020 (approximately 24 years).

All primary incident cancers except non-melanoma skin cancer

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

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

Measured using coronary artery calcification (CAC).

Outcome measures

Outcome measures
Measure
1 Original Lifestyle
n=701 Participants
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.
2 Original Metformin
n=679 Participants
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=681 Participants
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Subclinical Atherosclerosis
Men
70.1 CAC geometric mean in AU
Interval 45.4 to 108.2
40.2 CAC geometric mean in AU
Interval 26.1 to 61.9
63.7 CAC geometric mean in AU
Interval 41.3 to 98.3
Subclinical Atherosclerosis
Women
6.0 CAC geometric mean in AU
Interval 4.1 to 8.8
6.1 CAC geometric mean in AU
Interval 4.2 to 9.0
5.3 CAC geometric mean in AU
Interval 3.6 to 7.8

SECONDARY outcome

Timeframe: 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 ).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: All randomized to DPP were included

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

Outcome measures

Outcome measures
Measure
1 Original Lifestyle
n=1079 Participants
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.
2 Original Metformin
n=1073 Participants
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=1082 Participants
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Mortality
158 Participants
152 Participants
143 Participants

Adverse Events

1 Original Lifestyle

Serious events: 472 serious events
Other events: 234 other events
Deaths: 88 deaths

2 Original Metformin

Serious events: 482 serious events
Other events: 274 other events
Deaths: 85 deaths

3 Original Placebo

Serious events: 492 serious events
Other events: 257 other events
Deaths: 83 deaths

Serious adverse events

Serious adverse events
Measure
1 Original Lifestyle
n=916 participants at risk
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.
2 Original Metformin
n=927 participants at risk
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=936 participants at risk
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
General disorders
Any SAE Report
51.5%
472/916 • Number of events 1099 • Until data lock of Jan 2014, average of 15 years of follow-up
52.0%
482/927 • Number of events 1122 • Until data lock of Jan 2014, average of 15 years of follow-up
52.6%
492/936 • Number of events 1103 • Until data lock of Jan 2014, average of 15 years of follow-up

Other adverse events

Other adverse events
Measure
1 Original Lifestyle
n=916 participants at risk
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.
2 Original Metformin
n=927 participants at risk
Metformin / Lifestyle, previously the metformin treatment group during DPP Group Lifestyle: Quarterly group lifestyle sessions Metformin: Administered as 850mg twice per day
3 Original Placebo
n=936 participants at risk
Group Lifestyle, previously placebo treated participants during DPP Group Lifestyle: Quarterly group lifestyle sessions
Musculoskeletal and connective tissue disorders
Sprains and fractures requiring medical attention
25.5%
234/916 • Until data lock of Jan 2014, average of 15 years of follow-up
29.6%
274/927 • Until data lock of Jan 2014, average of 15 years of follow-up
27.5%
257/936 • Until data lock of Jan 2014, average of 15 years of follow-up

Additional Information

Marinella Temprosa, PI of Coordinating Center

George Washington University

Phone: 3018819260

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place