The Effects of Glucagon-Like Peptide-1 Receptor Agonists on
Atherosclerotic Plaque: Cytokine Profile in Diabetic Individuals
Abstract
Introduction: Type 2 diabetes mellitus (T2DM) represents one of the most
pressing global health challenges. The diabetic population has surged
dramatically, from 108 million in 1980 to an estimated 529 million in
2021. Hyperglycemia is intricately linked with endothelial dysfunction,
which contributes to the development of atherosclerosis, thereby
increasing the risk of cardiovascular diseases. Atherosclerotic
cardiovascular disease (ASCVD) is closely associated with vulnerable
plaques, influenced by numerous cytokines. Consequently, contemporary
diabetes treatments must consider pleiotropic effects that mitigate
cardiovascular risk. Objectives: This study aimed to investigate the
impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on
biomarkers indicative of atherosclerotic plaque instability, including
pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9),
and lipoprotein(a) [Lp(a)]. Patients and Methods: Fifty subjects
aged 41–81 years (mean: 60.7) with diagnosed T2DM (median HbA1c:
8.75%), dyslipidemia, and confirmed atherosclerosis via B-mode
ultrasound were included. All subjects were eligible to initiate
treatment with a GLP-1 RA. Results: Following a 180-day intervention
with GLP-1 RAs, our study observed a statistically significant decrease
in biochemical markers associated with atherosclerotic plaque
instability, including PTX3, CPC, and MMP-9 (p < 0.001), as
well as Lp(a) (p < 0.05). Conclusions: GLP-1 receptor agonists
significantly reduce concentrations of PTX3, CPC, MMP-9, and Lp(a), all
implicated in plaque vulnerability. This effect may contribute to the
reduction of cardiovascular risk among diabetic patients.