Impact of glucagon-like peptide-1 receptor agonism-based therapies on limb outcomes in peripheral artery disease and type 2 diabetes: An updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonism (GLP1RA)-based therapies (GLP1RA-BTs) form the cornerstone for managing type 2 diabetes (T2D) and obesity. However, their impact on limb-specific outcomes in peripheral artery disease (PAD) remains unclear. This systematic-review and meta-analysis evaluated the safety and efficacy of GLP1RA-BTs on limb outcomes in PAD and T2D. MATERIALS AND METHODS: Electronic databases were searched for studies involving GLP1RA-BTs in PAD and/or T2D. Primary outcome was the major adverse limb events (MALEs). Secondary outcomes were all-cause mortality, revascularization, amputation, major adverse cardiovascular events (MACE), cardiovascular mortality, myocardial infarction (MI), stroke, hospitalization for heart-failure (HHF), and amputations. Analyses were performed separately for studies exclusively enrolling patients with PAD (PAD cohort) and for those in broader T2D populations reporting limb outcomes but not limited to PAD, in which PAD comprised <15% of participants (T2D cohort). RESULTS: Data from 10 studies for PAD cohort (352 743 patients) and 7 studies for T2D cohort (1 759 799 patients) were analysed. In PAD cohort, MALE [OR 0.66 (0.44, 1.00); p = 0.05; I = 94%], all-cause mortality [OR 0.55 (0.38, 0.78); p = 0.0008; I = 97%], MACE [OR 0.68 (0.52, 0.88); p = 0.004; I = 85%], and MI [OR 0.68 (0.51, 0.91); p = 0.009; I = 42%] were lower in patients on GLP1RA-BTs compared to controls. In the PAD cohort, need for revascularization was significantly lower in GLP1RA-BTs than in controls [OR 0.85 (0.80, 0.90); p < 0.001; I = 0%]. In the T2D cohort, MALE [OR 0.70 (0.57, 0.85); p = 0.0005; I = 0%], amputations [OR 0.58 (0.48, 0.69); p < 0.001; I = 0%], and all-cause mortality [OR 0.55 (0.43, 0.69); p < 0.001; I = 85%] were significantly lower in GLP1RA-BT compared to controls. CONCLUSIONS: GLP1RA-BTs are beneficial in PAD, especially in reducing the need for revascularization.