Peripheral artery disease (PAD) carries high risks of limb loss, cardiovascular events, and death, yet the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide on vascular outcomes in this population has remained uncertain. A systematic review and meta-analysis published in Diabetes Metabolism Research and Reviews found that GLP-1-based therapies were associated with lower risks of major adverse limb and cardiovascular outcomes in real-world PAD populations.

A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies evaluating GLP-1–based therapies in adults with PAD. Six eligible studies involving more than 240,000 patients were included in the pooled analysis. Outcomes of interest included major adverse limb events (MALE), major adverse cardiovascular events (MACE), stroke, myocardial infarction, and all-cause mortality.

GLP-1-based therapies were associated with a significant 41% lower risk of MALE (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.39-0.90), although heterogeneity across studies was substantial. MACE risk was reduced by 33% (HR 0.67; 95% CI 0.53-0.85), with more consistent findings in diabetes populations. Stroke risk was also significantly lower (HR 0.75; 95% CI 0.63-0.89), with consistent effects across studies. Myocardial infarction and all-cause mortality were significantly reduced, though effect sizes varied between reports.

These findings suggest a broader vascular protective profile for GLP-1-based therapies in PAD, particularly among patients with diabetes, where consistency of benefit appeared stronger.