Cardiovascular and limb outcomes with SGLT2 inhibitors in patients with diabetes following peripheral endovascular therapy

Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for patients with diabetes mellitus (DM) and peripheral artery disease (PAD), their effects on limb-related outcomes remain uncertain, and their use after peripheral endovascular therapy (EVT) yields suboptimal outcomes. This study was to evaluate the prognostic impact of SGLT2i use in patients undergoing EVT for symptomatic PAD.

We retrospectively analyzed 470 PAD and DM patients (without end-stage renal disease) who underwent successful EVT between September 2016 and July 2022, categorizing them as SGLT2i users (n = 99) or non-users (n = 371). The primary endpoint was major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, or stroke), and the secondary endpoint was limb-level major adverse limb events (L-MALE: repeat revascularization or major amputation for the target limb). Propensity score matching was performed.

During a median follow-up of 4.0 years (interquartile range, 2.3-5.6), 115 MACE (100 deaths, 14 myocardial infarctions, 16 strokes) and 131 L-MALE (94 target-lesion revascularizations, 7 major amputations) occurred. Freedom from MACE was significantly higher in SGLT2i users than non-users (77.2% vs. 67.1%; p = 0.023), whereas freedom from L-MALE did not significantly differ between the two groups (52.8% vs. 57.5%; p = 0.59). These associations remained consistent across advanced age, frailty, and chronic limb-threatening ischemia (CLTI), heart failure (HF), and overweight status (all interactions p > 0.05).

In PAD and DM patients after successful EVT, SGLT2i use was linked to lower MACE risk without increased L-MALE, irrespective of age, frailty, CLTI, HF, and overweight status.