Long‐Term Outcomes of Glucagon‐Like Peptide‐1 Receptor Agonists in Patients With Peripheral Artery Disease and Type 2 Diabetes

Background Peripheral artery disease (PAD) affects >236 million people globally, particularly among those with type 2 diabetes. GLP‐1 (glucagon‐like peptide‐1) receptor agonists (GLP‐1 RAs) offer cardiovascular and kidney benefits, but their impact on PAD‐specific outcomes is underexplored. This study evaluates long‐term GLP‐1 RA effects on adverse outcomes in this population. Methods A retrospective cohort study using the TriNetX platform (January 1, 2010–January 1, 2025) included patients with both PAD and type 2 diabetes prescribed either GLP‐1 RAs or metformin, excluding those with recent cardiovascular events, end‐stage renal disease, or prior amputations. Propensity score matching was performed to account for confounding. Outcomes at 5 years included mortality, myocardial infarction, hospitalization, stroke, revascularization, amputations, dialysis, major adverse cardiovascular events, and kidney events. Results After matching, 2133 patients per cohort were analyzed in the overall group with PAD. At 5 years, GLP‐1 RA therapy was associated with lower mortality (10.31% versus 14.49%; hazard ratio [HR], 0.74 [95% CI, 0.62–0.88]; P =0.0005), hospitalization (69.3% versus 74.7%; HR, 0.87 [95% CI, 0.81–0.94]; P =0.0002), revascularization (4.69% versus 7.27%; HR, 0.64 [95% CI, 0.50–0.82]; P =0.0004), major amputation (2.30% versus 4.36%; HR, 0.52 [95% CI, 0.37–0.74]; P =0.0002), and minor amputation (4.03% versus 6.42%; HR, 0.63 [95% CI, 0.48–0.83]; P =0.0007). major adverse cardiovascular events, myocardial infarction, stroke, and major adverse kidney events were similar between groups. Conclusions GLP‐1 RAs were associated with lower rates of mortality, major amputation, revascularization, and hospitalization in PAD and type 2 diabetes patients. These findings support prioritizing GLP‐1 RAs for limb‐specific and cardiovascular outcomes in this high‐risk group.