Novel antidiabetic therapies in patients with peripheral artery disease: current perspective

Abstract

Peripheral artery disease (PAD) is the third leading cause of atherosclerosis-related morbidity, after coronary and cerebrovascular diseases. Approximations of its prevalence are 10-26% in the general adult population and increase with age. PAD bears the burden of functional decline and major adverse limb events (MALE), consisting of chronic limbthreatening ischemia, acute limb ischemia, and major amputations. Chronic limbthreatening ischemia is associated with 20% mortality and amputations in one year. The lifetime risk of PAD varies based on traditional risk factors, including diabetes, smoking, dyslipidaemia, hypertension, and a sedentary lifestyle. Chronic inflammation, metals, air pollution, and depression also seem to play a role. Furthermore, albuminuria is related to leg amputations and retinopathy is associated with chronic limb-threatening ischemia and PAD, regardless of the duration of diabetes and hemoglobin A1c (HbA1c) levels (1). PAD also has an increased propensity not only for MALE, but also for significant major adverse cardiovascular events (MACE). Coronary artery disease is prevalent in 30-50% of patients with PAD, while the presence of polyvascular disease further increases susceptibility to MACE (2).Diabetes significantly increases the risk of PAD, affecting 20-28% of people with diabetes. PAD is also a crucial risk factor for diabetic foot ulcers, and 50% of those with diabetic foot ulcers have PAD. The diagnosis of PAD and chronic limb-threatening ischaemia in diabetes is challenging due to atypical symptoms, particularly the absence of intermittent claudication and rest pain attributed to peripheral neuropathy, and medial artery calcification that affects the precision of non-invasive diagnostic tests. In people with diabetes, the progression of PAD differs from that of individuals without diabetes, manifesting itself in more distal arteries, affecting multiple bilateral arterial segments, and reducing collateral growth, thus increasing the risk of amputation. PAD in people with diabetes leads to worse outcomes, including non-healing foot ulcers, gangrene, amputation,