Beyond Glycemic Control: Organ-Protective Effects and Safety Profile of GLP-1 Receptor Agonists – A Comprehensive Review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have evolved from glucose-lowering agents for type 2 diabetes (T2D) into multifunctional therapies with effects extending across multiple metabolic and organ systems. This review summarizes current evidence regarding the pleiotropic effects, safety profile, and future therapeutic potential of GLP-1–based therapies beyond diabetes and obesity. Clinical evidence indicates that GLP-1RAs, particularly semaglutide, may reduce cardiovascular events and slow kidney disease progression, while also improving outcomes in heart failure with preserved ejection fraction. Beneficial effects have additionally been reported in metabolic dysfunction-associated steatohepatitis, osteoarthritis, obstructive sleep apnea, and peripheral artery disease. Emerging evidence suggests potential neuroprotective effects, although the role of GLP-1–based therapies in neurodegenerative diseases remains under investigation. Despite their generally favorable safety profile, gastrointestinal adverse events are common, while pancreatic, biliary, renal, ophthalmic, and other less frequent complications require appropriate clinical monitoring. The development of dual and triple receptor agonists, including tirzepatide, retatrutide, CagriSema, and amycretin, may further enhance weight loss and metabolic efficacy. Future treatment strategies may increasingly incorporate personalized selection of receptor profiles based on metabolic phenotype, comorbidities, therapeutic goals, and individual tolerability. Overall, GLP-1–based therapies represent an expanding therapeutic platform with potential applications extending well beyond glycemic control and weight management, although long-term clinical trials are required to establish their efficacy, safety, and organ-protective effects across broader patient populations.