Lifestyle modification and novel pharmacological treatment options for patients with peripheral arterial disease

Advancements in translational research and an increasingly refined understanding of the pathophysiological mechanisms underlying vascular and metabolic diseases have contributed to the emergence of novel therapeutic strategies in patients with peripheral artery disease (PAD). Among these, growing attention has been directed towards the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and to a lesser extent glucagon-like peptide-2 (GLP-2), as adjuncts to conventional therapy. Beyond their glucose-lowering properties, these agents exhibit cardioprotective, cytoprotective, vasoprotective and anti-inflammatory effects, along with beneficial modulation of microcirculation and exercise tolerance. This narrative review aims to synthesise clinical, obser-vational and experimental data regarding the impact of GLP-1 and GLP-2 receptor agonists on cardiovascular risk and functional parameters in patients with T2DM and PAD. The analysis integrates the 2024 European Society of Cardiology (ESC) guidelines for PAD management, which emphasise the "four pillars" of treatment and introduces the concept of GLP-1 RAs as a potential "fifth pillar" in an integrated therapeutic approach. Particular attention is devoted to mechanisms of action, effects on intermittent claudication symptoms, and the potential to improve quality of life in a population characterised by extreme vascular risk.