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Glp-1 Receptor Agonists Are Associated With Reduced Risk Of Mace And Mortality After Lower Extremity Revascularization In Patients With Diabetes
Ashwin K. Chetty, BS, Uma D. Alappan, Warren Carter, Nicholas Wells, Dana Alameddine, MD, Silvio Inzucchi, MD, Carlos Mena-Hurtado, MD, Edouard Aboain, MD, Raul J. Guzman, MD, Cassius Iyad Ochoa Chaar, MD.
Yale School of Medicine, New Haven, CT, USA.
OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are glucose-lowering and anti-obesity agents that have cardio-protective effects. There are limited data on GLP-1RA effects in patients with type 2 diabetes (DM) treated for peripheral arterial disease (PAD). We evaluated the impact of GLP-1RAs in patients with DM undergoing lower extremity revascularization (LER) for PAD accounting for glycemic control and concurrent insulin use.
METHODS: A retrospective review of patients with DM undergoing LER for PAD from 2013 to 2024 in a tertiary care center was performed. Characteristics of patients on a GLP-1RA prior to the index revascularization were compared to patients not treated with GLP-1RA. After 3:1 propensity matching, perioperative and long-term outcomes were compared. Kaplan Meier curves were used to assess time to major adverse limb events (MALE), major adverse cardiovascular events (MACE), cerebrovascular events (CVE), and mortality.
RESULTS: 1,537 patients with DM underwent LER with 12% on GLP1RA prior to index surgery. Patients receiving a GLP-1RA were significantly younger (64.2 vs 69.6, P<0.001), had higher mean BMI (32.1 vs 28.7, P<0.001) and more often on insulin (86.5% vs 56.6%, P<0.001). After matching (n=519 no GLP-1RA; n=174 GLP-1RA), there were no significant differences in baseline demographics, comorbidities or insulin use. Most patients underwent endovascular LER (89%) for chronic limb-threatening ischemia (65.7%). Preoperative mean HbA1C was significantly higher in patients on GLP-1RA (8.95% vs 8.28%, P<0.01). There was no significant difference in perioperative outcomes between groups. After a mean follow-up of 2.63 years for those on GLP-1RA and 3.9 years for those not, patients on GLP-1RA had significantly lower cumulative incidence of MALE (39.9% vs 50.0%, P=0.021), reintervention (35.1% vs. 45.5%, P=0.016), MACE (28.9% vs 40.7%, P=0.006), MI (11.6% vs. 27.4%, P<0.001), and mortality (22.4% vs 41.9%, P<0.001). Kaplan Meier analysis demonstrated significantly lower MACE and mortality in patients on GLP-1RA (figure), and CVE (P=0.046) but not MALE. A1C level remained higher in patients treated with GLP-1RA (7.95 vs 7.56, P=0.016) on last follow up.
CONCLUSIONS: Pre-operative GLP-1RA use is associated with reduced risk of MACE, CVE, and mortality in patients with DM following LER. The protective effect appears independent of glycemic control.
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