Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process

Int J Mol Sci. 2024 Feb 3;25(3):1854. doi: 10.3390/ijms25031854.

Abstract

Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1β (Il-1β) and tumor necrosis factor α (TNFα) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41-81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFα and Il-1β) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk.

Keywords: GLP-1; Il-1; TNFα; atherosclerosis; atherosclerotic plaque; dulaglutide; oxLDL; semaglutide.

MeSH terms

  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Biomarkers
  • Cytokines / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dyslipidemias* / drug therapy
  • Glucagon-Like Peptide-1 Receptor Agonists* / pharmacology
  • Glucagon-Like Peptide-1 Receptor Agonists* / therapeutic use
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Interleukin-1beta / therapeutic use
  • Plaque, Atherosclerotic* / drug therapy
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Biomarkers
  • Cytokines
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Glucagon-Like Peptide-1 Receptor Agonists

Grants and funding

This research was funded by the Medical University of Silesia, grant number PCN-1-227/N/2/O.