The Effects of New Antidiabetic Drugs on the Course of Peripheral Arterial Occlusive Disease

Peripheral arterial occlusive disease (PAOD) and diabetic foot syndrome (DFS) are the leading reasons for lower-limb amputation. The new antidiabetic drugs-GLP-1 receptor agonists (GLP-1-RA) and SGLT-2 inhibitors (SGLT-2-I)-improve glycemic control and lower the risk of cardiovascular events. The differing effects of these two drug classes on PAOD are currently under discussion.

This narrative review is based on pertinent publications retrieved by a selective PubMed search employing the terms "peripheral arterial disease," "SGLT-2 inhibitors," and "GLP-1 receptor agonists."

No randomized controlled trials (RCTs) of the use of SGLT-2 inhibitors and GLP-1 receptor agonists have yet been conducted in which amputation served as a primary endpoint; in the published trials, amputation is reported only as an adverse event. The SGLT-2 inhibitors empagliflozin and dapagliflozin, which are approved in Germany, were not associated with a significantly increased risk of amputation in RCTs. In one RCT, the GLP-1 receptor agonist semaglutide led to a median prolongation of maximum walking distance by 26.4 m in patients with PAOD. Evidence suggests that GLP-1 receptor agonists may improve the clinical course of PAOD.

The available evidence concerning the effect of GLP-1 receptor agonists and SGLT-2 inhibitors on the course of peripheral arterial occlusive disease (PAOD) and diabetic foot syndrome is limited. At any rate, no evidence suggests that GLP-1-RAs or SGLT-2 inhibitors worsen the course of PAOD or increase the risk of amputation. In the authors' judgment, the cardioprotective and nephroprotective effects of these drugs justify their use in patients with diabetic foot syndrome and PAOD.