Trial Outcomes & Findings for Improve PAD PERformance With METformin (NCT NCT03054519)
NCT ID: NCT03054519
Last Updated: 2026-08-24
Results Overview
Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
202 participants
Primary outcome timeframe
Change from baseline to six-month follow-up
Results posted on
2026-08-24
Participant Flow
Participant milestones
| Measure |
Metformin
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Overall Study
STARTED
|
97
|
105
|
|
Overall Study
COMPLETED
|
81
|
98
|
|
Overall Study
NOT COMPLETED
|
16
|
7
|
Reasons for withdrawal
| Measure |
Metformin
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
12
|
5
|
|
Overall Study
Death
|
2
|
1
|
|
Overall Study
Missed follow-up testing
|
2
|
1
|
Baseline Characteristics
Improve PAD PERformance With METformin
Baseline characteristics by cohort
| Measure |
Metformin
n=97 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=105 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
Total
n=202 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.9 years
STANDARD_DEVIATION 9.0 • n=1541 Participants
|
69.3 years
STANDARD_DEVIATION 7.8 • n=1121 Participants
|
69.6 years
STANDARD_DEVIATION 8.4 • n=2662 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=1541 Participants
|
24 Participants
n=1121 Participants
|
56 Participants
n=2662 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=1541 Participants
|
81 Participants
n=1121 Participants
|
146 Participants
n=2662 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=1541 Participants
|
5 Participants
n=1121 Participants
|
8 Participants
n=2662 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
92 Participants
n=1541 Participants
|
96 Participants
n=1121 Participants
|
188 Participants
n=2662 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=1541 Participants
|
4 Participants
n=1121 Participants
|
6 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=1541 Participants
|
0 Participants
n=1121 Participants
|
0 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=1541 Participants
|
0 Participants
n=1121 Participants
|
2 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=1541 Participants
|
0 Participants
n=1121 Participants
|
1 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
Black or African American
|
41 Participants
n=1541 Participants
|
38 Participants
n=1121 Participants
|
79 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
White
|
52 Participants
n=1541 Participants
|
64 Participants
n=1121 Participants
|
116 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=1541 Participants
|
0 Participants
n=1121 Participants
|
0 Participants
n=2662 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=1541 Participants
|
3 Participants
n=1121 Participants
|
4 Participants
n=2662 Participants
|
|
Ankle brachial index, consisting of a ratio of Doppler recorded pressures.
|
0.63 Ratio
STANDARD_DEVIATION 0.16 • n=1541 Participants
|
0.66 Ratio
STANDARD_DEVIATION 0.15 • n=1121 Participants
|
0.64 Ratio
STANDARD_DEVIATION 0.16 • n=2662 Participants
|
|
Body mass index
|
28.7 kg/m^2
STANDARD_DEVIATION 6.6 • n=1541 Participants
|
28.6 kg/m^2
STANDARD_DEVIATION 5.8 • n=1121 Participants
|
28.6 kg/m^2
STANDARD_DEVIATION 6.2 • n=2662 Participants
|
|
Six-minute walking distance
|
359.2 meters
STANDARD_DEVIATION 83.0 • n=1541 Participants
|
357.0 meters
STANDARD_DEVIATION 105.6 • n=1121 Participants
|
358.0 meters
STANDARD_DEVIATION 95.2 • n=2662 Participants
|
PRIMARY outcome
Timeframe: Change from baseline to six-month follow-upParticipants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes
Outcome measures
| Measure |
Metformin
n=81 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=98 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Six-minute Walk Performance
|
9.95 meters
Standard Error 11.42
|
8.82 meters
Standard Error 10.29
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upA Gardner treadmill exercise protocol will be used
Outcome measures
| Measure |
Metformin
n=36 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=43 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Maximal Treadmill Walking Time
|
1.54 minutes
Standard Error 1.20
|
2.31 minutes
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Percent change from baseline to six-month follow-upUpper brachial artery flow-mediated dilation was evaluated by measuring percent change in the brachial artery diameter in response to reactive hyperemia, induced by inflating a blood pressure cuff for five minutes over the brachial artery.
Outcome measures
| Measure |
Metformin
n=33 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=42 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Brachial Artery Flow-mediated Dilation
|
-0.25 percent change
Standard Error 1.07
|
-0.21 percent change
Standard Error 0.96
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upThe Walking impairment questionnaire is a patient reported outcome measure, in which participants indicate the ease of walking distances ranging from across the room to up to approximately 1500 feet. The score is calculated on a 0-100 scale, where 0 indicates the in ability to walk any of the distances and 100 indicates no difficulty walking any of the distances.
Outcome measures
| Measure |
Metformin
n=82 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=96 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
The Walking Impairment Questionnaire - Distance Score
|
5.35 score on a scale
Standard Error 4.45
|
0.91 score on a scale
Standard Error 4.03
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upThis outcome is a patient reported quality of life measure. The score ranges from 0 to 100, where 0 indicates extremely poor functioning and 100 indicates the best possible functioning,
Outcome measures
| Measure |
Metformin
n=82 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=97 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
The SF-36 Physical Functioning Score
|
-1.62 score on a scale
Standard Error 3.65
|
-2.34 score on a scale
Standard Error 3.30
|
SECONDARY outcome
Timeframe: Change from baseline to six-month follow-upCapillary density was measured as the number of capillaries per mm2 of muscle.
Outcome measures
| Measure |
Metformin
n=9 Participants
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=10 Participants
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
Calf Muscle Biopsy Biochemical Measures - Capillary Density
|
0.11 capillaries/mm^2
Standard Error 0.30
|
0.22 capillaries/mm^2
Standard Error 0.28
|
Adverse Events
Metformin
Serious events: 11 serious events
Other events: 76 other events
Deaths: 2 deaths
Placebo
Serious events: 14 serious events
Other events: 72 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Metformin
n=97 participants at risk
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=105 participants at risk
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
General disorders
Coronary revascularization
|
1.0%
1/97 • Number of events 1 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
0.00%
0/105 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Cardiovascular death
|
2.1%
2/97 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
0.00%
0/105 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Non-cardiac death
|
0.00%
0/97 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
0.95%
1/105 • Number of events 1 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Heart failure
|
0.00%
0/97 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
1.9%
2/105 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Infection
|
0.00%
0/97 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
0.95%
1/105 • Number of events 1 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Lower extremity revascularization
|
1.0%
1/97 • Number of events 1 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
2.9%
3/105 • Number of events 3 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Arrhythmia
|
2.1%
2/97 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
1.9%
2/105 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Cardiovascular event
|
3.1%
3/97 • Number of events 3 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
1.9%
2/105 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Peripheral artery disease
|
0.00%
0/97 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
1.9%
2/105 • Number of events 2 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Other
|
4.1%
4/97 • Number of events 4 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
5.7%
6/105 • Number of events 9 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
Other adverse events
| Measure |
Metformin
n=97 participants at risk
Metformin daily
Metformin: Participants will be prescribed up to 2,000 mgs daily of metformin
|
Placebo
n=105 participants at risk
Placebo daily for six months.
Placebo: Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.
|
|---|---|---|
|
General disorders
Nausea
|
33.0%
32/97 • Number of events 73 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
26.7%
28/105 • Number of events 52 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Vomit
|
17.5%
17/97 • Number of events 26 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
12.4%
13/105 • Number of events 21 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Abdominal discomfort or pain
|
43.3%
42/97 • Number of events 109 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
31.4%
33/105 • Number of events 74 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Indigestion or an upset stomach
|
62.9%
61/97 • Number of events 155 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
39.0%
41/105 • Number of events 97 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
|
General disorders
Headache
|
36.1%
35/97 • Number of events 108 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
47.6%
50/105 • Number of events 104 • Adverse events data were collected monthly from baseline to 6-month follow-up.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place