Glucagon-like peptide-1 receptor agonists are associated with fewer major adverse cardiovascular and limb events in patients with moderate peripheral arterial disease.

Objective: Patients with peripheral arterial disease (PAD) and diabetes mellitus have significantly higher rates of cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RA)-such as tirzepatide and semaglutide-have been shown to decrease rates of major adverse cardiac events (MACEs) and mortality in patients with diabetes mellitus. However, their effect on limb outcomes in patients with PAD has yet to be investigated. The aim of this study was to explore the impact of GLP-1RAs on cardiovascular outcomes in patients with moderate PAD.

Methods: Data were sourced from the TriNetX research network, encompassing more than 1002 health care organizations. We used a one:one propensity-matched study to compare patients with an ankle-brachial index (ABI) of 0.4-0.9 who were started on GLP-1RA (group 1) with those patients who were not started on a GLP-1RA (group 2). Patients with chronic wounds or with an ABI outside of this range were excluded. MACEs were defined as myocardial infarction, stroke, acute ischemic heart disease, and heart failure. Major adverse limb events (MALEs) were defined as acute limb ischemia requiring thrombectomy or major amputation. Any inpatient admission, MACE, and MALE were identified using International Classification of Diseases, 10the edition, codes. Standard statistical methods were used as appropriate.

Results: We identified 858,750 patients with moderate PAD between October 1, 2022, and December 31, 2023. After matching for age, sex, diabetes status, smoking history, and coronary artery disease, each group included 55,041 patients. Group 1 had a higher starting weight (216 ± 56.8 lb versus 188 ± 51.5 lb; P = .0001) and baseline hemoglobin A1C (7.2 ± 1.8 versus 6.7 ± 1.7; P = .01). The baseline ABI was 0.73 ± 0.29 in group 1 and 0.88 ± 0.26 in group 2 (P = .07). At 1 year, there were fewer mortalities (1.7% versus 4.4%; P < .01), MACEs (25.4% versus 29.3%; P < .01), MALEs (0.8% versus 1.5%; P < .01), and inpatient hospitalizations (17.9% versus 26.8%; P < .01) in group 1. On multivariate analysis, GLP-1RAs significantly reduced the risk of MACEs (hazard ratio, 0.87; 95% CI, 0.85-0.89; P = .01), MALEs (hazard ratio, 0.57; 95% confidence interval [CI], 0.51-0.64; P = .02), and inpatient admission (odds ratio, 0.64; 95% CI, 0.62-0.66; P = .01) and complications (odds ratio, 0.67; 95% CI, 0.65-0.68; P = .01).

Conclusions: The use of GLP-1RAs in patients with moderate PAD is associated with a decreased rate of MACEs and MALEs. Patients on GLP-1RAs are at a decreased risk of mortality, inpatient hospitalizations, and inpatient complications.