Beyond glycemic control: emerging therapeutic applications of GLP-1 receptor agonists: a comprehensive narrative review

Abstract

The therapy of type 2 diabetes mellitus and obesity has been changed by glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, clinical evidences suggest their therapeutic potential extends far beyond glycaemic management with major function in cardiovascular, hepatic, renal and neurological illnesses To give a complete appraisal of the emerging non-glycaemic therapeutic potential of GLP-1 RAs through a survey of the available clinical evidence and to highlight future research options in this rapidly growing field. A thorough literature search was performed in the PubMed, Scopus and Google Scholar databases from inception to November 2025. The search criteria included GLP-1 receptor agonists, semaglutide, tirzepatide, and combinations with specified therapeutic areas. Clinical trials, systematic reviews and mechanistic research of landmark importance were prioritized GLP-1 RAs have shown important cardiovascular benefits, decreasing major adverse cardiovascular events (MACE) by 20%. Tirzepatide reduced heart failure hospitalization by 38% in patients with heart failure with intact ejection fraction. These medicines show potential for decreasing hepatic steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease . Observational studies demonstrate a 48% reduction in incidence of dementia and growing evidence suggests neuroprotective effects. Other therapeutic uses are for chronic renal disease, polycystic ovary syndrome, obstructive sleep apnoea and substance use disorders. GLP-1 RAs represent a paradigm change in pharmacology, evolving from glucose-lowering to multi-organ protecting treatments. The development of multiple and triple agonists and oral non-peptide formulations will certainly greatly enhance their clinical value.