Beyond Glycemic Control: GLP-1RA–Based Therapies and Emerging Targets Beyond the Metabolic Axis

Background/Objectives: Modern diabetes therapy extends beyond glycemic control and increasingly focuses on comprehensive risk reduction to prevent long-term complications, improve quality of life, and reduce premature mortality. Accordingly, modern therapeutic approaches address not only glucose metabolism but also cardiovascular, renal, and metabolic consequences of diabetes. Within this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a significant therapeutic class. In addition to their well-known effects on glycemic control and the metabolic-cardiovascular-renal axis, increasing evidence suggests that these agents may exert a range of pleiotropic effects and opening new therapeutic venues, discussed in this review. Methods: A narrative review of the literature was conducted using the PubMed, Scopus, and Google Scholar databases. Publications from 2014 and 2026 were screened using predefined keywords related to GLP-1 RAs and their potential effects across multiple physiological systems and diseases. Notably, more than 80% of the included studies were published between 2020 and 2026, reflecting the recent growth of research in this field. Results: GLP-1 RAs have been associated with beneficial effects across a wide range of conditions, including substance use disorders, mental health disorders, neurodegenerative diseases, obesity-related complications, liver disease, genitourinary disorders, osteoarthritis, and sleep apnea. While they are currently the most effective pharmacological agents for the treatment of obesity, they also significantly reduce hepatic steatosis and are associated with a decreased risk of developing hepatocellular carcinoma. Furthermore, they have also demonstrated positive effects against prostate cancer, polycystic ovary syndrome (PCOS), improved libido and fertility. Conclusions: GLP-1 RAs should no longer be regarded solely as antihyperglycemic agents. Instead, they represent a versatile therapeutic class with expanding clinical relevance across multiple medical disciplines. While current evidence is promising, further large-scale, well-designed clinical trials are required to define their full therapeutic potential.