GLP-1 receptor agonists and coronary plaques regression in diabetic patients after acute coronary syndromes
Mauro Gitto, Federica Catapano, Marco Francone, Gianluca Mincione, Vincenzo Scialò, Carlo Andrea Pivato, Costanza Lisi, Damiano Regazzoli, Davide Cao, Roberta Maria Fiorina, Alessandra Petrelli, Loredana Bucciarelli, Cristian Loretelli, Gianluigi Condorelli, Paolo Fiorina, Giulio Stefanini
Abstract
BACKGROUND: Despite advances in therapeutic strategies a significant proportion of acute coronary syndrome (ACS) patients experience early coronary artery disease (CAD) progression, particularly those with diabetes. AIM: To evaluate CAD progression in diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1Ra) over 1 year after an ACS. METHODS: Patients presenting with non-ST-elevation ACS between 2019 and 2022 were enrolled in a prospective registry and underwent serial coronary computed tomography angiography (CCTA) at baseline (after revascularization, during the index hospitalization) and at 1-year follow-up. The primary endpoint was the absolute change (1 year - baseline) in non-culprit lesion plaque burden (ΔPB) on CCTA, with the absolute change in patient percent atheroma volume (ΔPAV) as a key secondary endpoint. A comprehensive lipidomic, metabolomic, and proteomic plasma assessment was also performed in all GLP-1Ra-treated patients and four randomly selected controls. RESULTS: Of 28 diabetic patients, 7 (25%) with 22 coronary plaques were treated with GLP-1Ra, and 21 (75%) with 65 plaques received other antidiabetic agents. In the 1-year observation frame, both ΔPB (-5.8 ± 12.8% vs. -1.1 ± 13.6%, p = 0.041) and ΔPAV (-6.1% [-7.3, -1.8] vs. -0.7% [-2.4, 9.8], p = 0.039) were significantly lower in GLP-1Ra-treated patients. Total atheroma volume also showed a numerically greater reduction in the GLP-1Ra cohort (0.7 mm³ [-2.5-8.7] vs. 25.0 mm³ [4.8-39.7]), primarily due to a decrease in plaque fibrofatty volume percentage (-2.9 ± 10.1% vs. 1.0 ± 6.8%, p = 0.042). Lipidomic, metabolomic, and proteomic analyses identified reductions in monoacylglycerols and triacylglycerols, increases in diacylglycerols and phosphatidylethanolamine, a shift from carbohydrate metabolism toward lipid metabolism and hormone regulation, and differential expression of proteins involved in complement activation, endothelial function, and cytoskeletal organization in GLP-1Ra-treated patients compared with controls. CONCLUSIONS: In diabetic patients with ACS, GLP-1Ra therapy was associated with a significant regression in coronary plaque burden at 1 year, supported by favorable lipidomic, metabolomic, and proteomic changes. These findings suggest a potential role for GLP-1Ra in modifying atherosclerosis progression beyond glycemic control.