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 aninclusion 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 ofPAD or angiographic evidence of PAD who have ischemic symptoms during the six-minutewalk and/or treadmill exercise stress test will be eligible.

• Fourth, potential participants with a history of lower extremity revascularizationwho do not meet the criterion above and have an ABI > 0.90 with a 20% or higher dropin 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 diagnoseddiabetes mellitus, b) use of one or more diabetes medications, c) two baselinehemoglobinA1C values of >6.5, d) two fasting glucose values >126 mg/dl. [NOTE: thesecond fasting glucose value and hemoglobin A1C values will be at the discretion ofthe principal investigator. For example, if the first glucose value is >300 or thefirst A1C value is >6.9, then investigators may decide not to repeat the value.]

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

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

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

• Planned lower extremity revascularization, orthopedic surgery, or other majorsurgery 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 diseaserequiring oxygen, Parkinson's disease, a life-threatening illness with lifeexpectancy less than six months, or cancer requiring treatment in the previous twoyears. [NOTE: potential participants may still qualify if they have had treatmentfor 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. However, investigatordiscretion may be used to allow some people below this threshold to participate, ifthe investigator determines there is another reason for their lower score, includinglack of familiarity with the English language or lack of sufficient education toachieve a score of 23 or higher. Note that the MMSE include some spelling andEnglish writing proficiency.

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