GLP-1 RECEPTOR AGONISTS AND THEIR PLEIOTROPIC EFFECTS: FROM METABOLIC THERAPY TO CARDIOVASCULAR AND RENAL PROTECTION

Abstract

The increasing prevalence of obesity, type 2 diabetes mellitus, and cardiovascular diseases has established cardiometabolic syndromes as one of the major challenges of contemporary medicine, driving the development of therapeutic strategies capable of targeting multiple pathophysiological mechanisms involved in cardiovascular and renal damage. In this context, glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for the treatment of type 2 diabetes mellitus, have gained prominence in cardiovascular and metabolic medicine due to their pleiotropic effects beyond glycemic control. The present study aimed to critically review the scientific evidence regarding the cardiometabolic, inflammatory, cardiovascular, and renal mechanisms associated with GLP-1RAs, as well as their contemporary applicability in cardiorenal-metabolic medicine. This study consists of a narrative literature review of a descriptive, analytical, and translational nature, conducted through bibliographic research in the PubMed/MEDLINE, SciELO, Virtual Health Library (VHL), Scopus, and Google Scholar databases, including original articles, reviews, meta-analyses, clinical guidelines, and major clinical trials published between 2020 and 2025. The findings demonstrated that GLP-1RAs promote systemic inflammatory modulation, reduction of oxidative stress, improvement of endothelial function, attenuation of atherosclerotic progression, renal protection, and improvement of metabolic profile. Major clinical trials, such as LEADER, SUSTAIN-6, REWIND, SELECT, and FLOW, demonstrated significant reductions in major cardiovascular events, cardiovascular mortality, and progression of chronic kidney disease, including benefits observed in individuals without established diabetes mellitus. It is concluded that GLP-1RAs represent one of the most relevant therapeutic innovations in contemporary cardiometabolic medicine, contributing to a paradigm shift in the integrated management of cardiovascular, metabolic, and renal diseases.