Sodium-glucose transporter-2 inhibitors: safety and efficacy in patients with peripheral artery disease

The objective of this review is to assess the safety and efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT-2is) in patients with peripheral arterial disease (PAD). A literature search of PubMed and EMBASE databases (through March 2025) was performed with MeSH words and phrases related to SGLT-2is AND PAD. Articles encompassing original research including results specifying safety and efficacy outcomes particularly in the PAD population were included. Narrative reviews or studies with lack of a substantial PAD population or relevant outcomes were excluded. Our literature search resulted in 289 articles of which 18 were included in the current review. Findings consistently highlighted the cardiovascular benefits SGLT-2is show in PAD patients, supporting their potential role in improving clinical outcomes. Most studies showed neutral or favorable safety regarding lower limb events, suggesting no more risk of adverse limb-related outcomes compared to the non-PAD population. Patients with PAD are likely to see improved outcomes and favorable safety with SGLT-2is, namely, canagliflozin, empagliflozin, and dapagliflozin. Observation of specific PAD populations also suggests that there is no higher risk of adverse limb events, including amputation risk, as compared to patients without PAD. Literature supports the safe and effective use of SGLT-2is in patients with concomitant PAD, regardless of the indication for use. Ongoing studies are needed to assess specific PAD outcomes with SGLT-2is and determine the specific mechanisms proposed for such benefits.