J Am Heart Assoc. 2026 Jul 1:e045664. doi: 10.1161/JAHA.125.045664. Online ahead of print.
ABSTRACT
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.
PMID:42383806 | DOI:10.1161/JAHA.125.045664