Cardiovascular, limb, and kidney effects of SGLT2 inhibitors in patients with peripheral artery disease: a systematic review and meta-analysis of randomized controlled trial data
Abstract
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) provide substantial cardiovascular benefits across a broad spectrum of patients at high atherosclerotic risk. However, evidence for their cardiovascular efficacy in patients with peripheral artery disease (PAD) remains limited. Accordingly, we conducted this systematic review and meta-analysis to synthesize available evidence and clarify the cardiovascular, limb, and kidney outcomes of SGLT2i in patients with PAD.
Methods: PubMed, Embase, and the Cochrane Library were searched from inception to 20 December 2025 for studies evaluating SGLT2i therapy in patients with PAD. The primary outcome was the composite of hospitalization for heart failure (HHF) or cardiovascular death. Secondary outcomes included HHF, cardiovascular death, amputation, composite renal outcomes, all-cause mortality, and major adverse cardiovascular events (MACE).
Results: Five studies comprising 7,275 patients with PAD were included. Among patients with PAD, SGLT2i therapy was associated with a lower risk of the composite of HHF or cardiovascular death (HR 0.73; 95% CI 0.64 to 0.83; p interaction >0.10). However, in exploratory subgroup analyses among patients with PAD, SGLT2i treatment for ≥ 2 years was associated with a numerically greater reduction in cardiovascular death (HR 0.73; 95% CI 0.60-0.90), whereas no clear effect was observed in trials with a duration of interaction = 0.06).
Conclusions: SGLT2i-therapy is associated with a…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,275 participants or records.
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