Effects of SGLT2 inhibitors and GLP1-receptor agonists on cardiovascular and limb events in peripheral artery disease: A review

Peripheral artery disease (PAD) and diabetes mellitus are two overwhelming health problems associated with major cardiovascular (CV) and limb events, in addition to increased mortality, despite advances in medical therapies including statins and renin-angiotensin system inhibitors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1-receptor agonists (GLP1-RA) are two new antihyperglycemic drug classes that have been associated with a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) and CV risk. Whereas most studies had enrolled patients with T2D and concurrent CV disease (CVD), patients with PAD were obviously underrepresented. Furthermore, there was a signal of increased risk of amputation in one of the main trials with canagliflozin. We aim to provide a general review of the current literature and summarize societal guideline recommendations addressing the role of SGLT2i and GLP1-RA drugs in patients with CVD focusing on the PAD population when data are available. Endpoints of interest were MACE and, when available, major adverse limb events (MALE).