Improve PAD PERformance With METformin

Inclusion Criteria:

All participants will have PAD. PAD will be defined as follows:

- First, an ankle brachial index (ABI) <0.90 at the baseline study visit is an inclusion
criterion for PAD.

- Second, potential participants who have an ABI > 0.90 but ≤ 1.00 and experience a 20%
or higher drop in ABI after heel-rise exercise will be eligible.

- Third, potential participants with an ABI > 0.90 who have vascular lab evidence of PAD
or angiographic evidence of PAD who have ischemic symptoms during the six-minute walk
and/or treadmill exercise stress test will be eligible.

- Fourth, potential participants with a history of lower extremity revascularization who
do not meet the criterion above and have an ABI > 0.90 with a 20% or higher drop in
ABI after heel-rise exercise will be eligible.

Exclusion Criteria:

- Above- or below-knee amputation.

- Critical limb ischemia.

- Wheelchair-bound or requiring a walker to ambulate.

- Walking is limited by a symptom other than PAD.

- Current foot ulcer on bottom of foot.

- Diabetes mellitus defined as one or more of a) patient report of physician diagnosed
diabetes mellitus, b) use of one or more diabetes medications, c) baseline
hemoglobinA1C value of >6.5, d) two fasting glucose values >126 mg/dl. [NOTE: the
second fasting glucose value will be at the discretion of the principal investigator.
For example, if the first value is >300, then investigators may decide not to repeat
the value.]

- Chronic kidney disease defined as GFR <45. [NOTE: if GFR is 40-44, investigator
discretion will be used to determine if a repeat test may be performed. If the second
GFR value is >45, the participant may be included.]

- Chronic liver disease defined as two or more hepatic function tests >2.0 times the
upper limit of normal. [NOTE: participants who meet this criterion may undergo a
re-test of hepatic function tests to determine whether initially elevated hepatic
enzymes represented a transient or spurious phenomenon.]

- Failure to successfully complete the 2-week study run-in, defined as unable to
tolerate metformin and/or failing to take the medication daily for 10 or more days in
the two-week period.

- Planned lower extremity revascularization, orthopedic surgery, or other major surgery
during the next six months.

- Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary
revascularization, or other major surgery in the previous three months.

- Major medical illness including renal disease requiring dialysis, lung disease
requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy
less than six months, or cancer requiring treatment in the previous two years. [NOTE:
potential participants may still qualify if they have had treatment for an early stage
cancer in the past two years and the prognosis is excellent. Participants who only use
oxygen at night may still qualify.]

- Mini-Mental Status Examination (MMSE) score <23 or dementia.

- Participation in or completion of a clinical trial in the previous three months.
[NOTE: after completing a stem cell or gene therapy intervention, participants will
become eligible after the final study follow-up visit of the stem cell or gene therapy
study so long as at least six months have passed since the final intervention
administration. After completing a supplement or drug therapy (other than stem cell or
gene therapy), participants will be eligible after the final study follow-up visit as
long as at least three months have passed since the final intervention of the trial.]

- Currently taking metformin or has taken metformin in past six months.

- Increase in angina or angina at rest

- Non-English speaking.

- Visual impairment that limits walking ability.

- In addition to the above criteria, investigator discretion will be used to determine
if the trial is unsafe or not a good fit for the potential participant.

Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized
persons) and adults unable to consent will not be included in the study.