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PAD is a widespread disease with an increasingly growing impact.A clear association between DM and macrovascular disease has been established.There is an unmet clinical need for CVD prevention in patients with DM and PAD.New anti-diabetic drug classes have shown CV benefit in high CVD risk patients.Ongoing trials will help to clarify the CV benefit and safety of new anti-diabetics.Diabetes-induced hyperglycemia is a causal factor for cardiovascular disease (CVD) and, specifically, peripheral artery disease (PAD). Metformin is the cornerstone drug therapy for glucose-lowering that exerts beneficial effects beyond glycemic control. New glucose-lowering drugs have recently been shown cardiovascular benefits and their impact on CVD risk is of increasing importance. Current guidelines recommend these novel therapies as second-line options for patients with diabetes and established CVD. Given the prevalence of CVD in this population, a complete understanding of the cardiovascular safety/efficacy of glucose-lowering drugs is needed. The present review provides an update overview of the anti-diabetic drugs and their impact on PAD and cardiovascular outcomes, summarizing key recent trial findings highlights their risk and benefits.