GLP-1 RECEPTOR AGONISTS: EXPANDING INDICATIONS FROM DIABETES AND OBESITY TO CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES

Glucagon-like peptide-1 receptor agonists have evolved from glucose-lowering agents for type 2 diabetes into therapies with broad metabolic, cardiovascular, and neuroprotective effects. This review examines the expanding therapeutic landscape of GLP-1 receptor agonists, including liraglutide, semaglutide, dulaglutide, and exenatide, as well as the dual GIP/GLP-1 receptor agonist tirzepatide. In type 2 diabetes, these agents improve glycemic control and have demonstrated cardiovascular benefits in large outcome trials such as LEADER, SUSTAIN-6, and REWIND. In obesity, higher doses of liraglutide and semaglutide produce clinically meaningful weight loss, and tirzepatide has shown unprecedented efficacy in the SURMOUNT-1 trial. Emerging evidence supports potential benefits in nonalcoholic steatohepatitis, chronic kidney disease, and neurodegenerative disorders including Parkinson's disease and Alzheimer's disease. Proposed mechanisms include weight reduction, improved insulin sensitivity, anti-inflammatory effects, and direct neuroprotection. Gastrointestinal adverse effects are common, and rare but serious events such as pancreatitis and medullary thyroid carcinoma remain concerns. This review critically evaluates the evidence through early 2023, highlights unresolved questions, and discusses future directions, including oral formulations, combination incretin-based therapies, and novel indications.