GLP1 Receptor Agonists—Effects beyond Obesity and Diabetes

Abstract

Glucagon-like peptide-1 receptor agonists (GLP1RA) have been transformative for patients and clinicians in treating type-2 diabetes and obesity. Drugs of this class, the bioavailability of which is continuously improving, enable weight loss and control blood glucose with minimal unwanted side effects. Since adopting GLP1RA for treating metabolic diseases, animal and clinical studies have revealed their beneficial effects on several other pathologies, including cardiovascular diseases, neurodegeneration, kidney disease, and cancer. A notable commonality between these diseases is their association with older age. Clinical trials and preclinical data suggest that GLP1RA may improve outcomes in these aging-related diseases. Some of the benefits of GLP1RA may be indirect due to their effects on obesity and glucose metabolism. However, there is building evidence that GLP1RA may also act directly on multiple organs implicated in aging-related pathology. This review aims to compile the studies reporting the effects of GLP1RA on aging-related diseases and discuss potential underlying mechanisms.

Healthcare on the brink: navigating the challenges of an aging society in the United States

“…The hope is that restoring immune health could translate to beneficial downstream effects on the vascular, heart, brain, and kidney systems. The advent of the GLP-1 drug class (e.g., Semaglutide and Tirzepatide), which not only have the potential to prevent obesity-related diseases later in life, also offers a promising avenue for the reversal of metabolic aging and may even promote DNA repair in neurodegenerative diseases 56 . Maintaining muscle function is also crucial, particularly in the context of aging or chronic conditions like sarcopenia 57 .…”

High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective

“…To sum up, the development of a GLP-1-GLP-1R-based mini GIBAC perspective represents a promising strategy for extracting electrostatic structural features from ligand-receptor complexes and advancing drug discovery efforts targeting the GLP-1/GLP-1R axis. By combining computational modeling with experimental validation, a GLP-1-GLP-1R-based mini GIBAC offers a powerful tool for elucidating the molecular basis of ligand recognition and receptor activation, paving the way for the development of next-generation therapeutics with improved efficacy and safety for patients with diabetes and/or obesity [14][15][16].…”

“…GLP-1, an incretin hormone secreted by enteroendocrine intestinal L-cells, exerts its physiological effects by binding to GLP-1R, a G-protein-coupled receptor predominantly expressed in pancreatic β-cells, among other tissues [11][12][13]. Activation of GLP-1R initiates a signaling cascade leading to enhanced insulin release, inhibition of glucagon secretion, and regulation of satiety, making it an attractive target for the treatment of type 2 diabetes and obesity [14][15][16].…”

Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease

“…Recently, researchers have been investigating how medications known as GLP-1RAs, primarily used in treating type 2 diabetes, might influence the kidneys and affect DKD progression [ 35 ]. The use of GLP-1RAs has been associated with improved kidney outcomes, including reduced albuminuria and preservation of the filtration rate.…”