Peripheral arterial disease (PAD) is a state of chronic systemic inflammation and atherosclerosis that results in the narrowing or occlusion of peripheral arteries, most commonly involving the legs. PAD affects up to 20% of older adults and is especially prevalent among Veterans due to a high rate of smoking. Nearly 90% of those with PAD suffer from intermittent claudication (IC), defined as reproducible muscle pain with activity due to reduced blood flow and is relieved with rest. Those with IC are at increased risk of cardiovascular (CV) morbidity and mortality with progressive decline in walking speeds and distance, functional independence, and health related quality of life (HRQoL). The treatment of IC beings with medical optimization with smoking cessation, aspirin and statin therapy, and exercise. Pharmacological therapies for IC are minimally effective. Supervised exercise therapy does improve walking distance and functional status but is not easily accessible, compliance is low, and the benefits are not durable. Ultimately, surgical revascularization is the only effective therapy that can reliably improve IC symptoms long-term but is invasive and expensive. Metformin is an inexpensive, safe, and effective treatment for Type 2 diabetes (DM2). It has numerous effects that can counteract the reactive oxygen species, systemic inflammation, DNA damage, and mitochondrial dysfunction that contribute to age related cellular and organ dysfunction. In preclinical studies, metformin also stimulates angiogenesis and reduces atherosclerotic calcification. Finally, metformin has been shown to reduce CV specific morbidity and mortality in those with DM2, independent of glucose control. Thus, we hypothesize that metformin may be an effective treatment for symptomatic PAD. We developed the MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC) Trial to evaluate the effect of metformin on functional status, PAD progression, systemic and vascular inflammation, neutrophil extracellular traps, exosomes and microRNAs, and mitochondrial function in nonDM2 Veterans with symptomatic PAD. The trial is a quadruple-blind, phase 3, single institution, randomized controlled trial which was developed with Veteran input and is based on patient centered outcomes. A total of 200 male and female Veterans with symptomatic PAD being evaluated at the VA Pittsburgh (VAPHS) vascular clinic will be stratified by maximum walking distance (MWD) on the 6-minute walk test (6MWT) and randomized 1:1 to 6 months of 1000mg of Metformin ER or placebo daily. This trial has 80% power to determine the effect on the primary outcome of MWD on the 6MWT at 6 months. Secondary outcomes include validated assessments of overall functionality, general and disease specific HRQoL, subclinical and clinical PAD progression (ankle brachial index, pulse volume recordings, and endothelial function by EndoPAT), changes in systemic inflammatory markers and systemic mitochondrial ef...