DRUG DESIGN INNOVATIONS IN METABOLIC DISORDERS: GLP-1 ANALOGUES AND BEYOND

Abstract- Type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and non-alcoholic fatty liver disease (NAFLD) are examples of metabolic diseases that cause a rapidly increasing health burden worldwide. Recent developments in drug design have resulted in the development of new therapeutic drugs targeting various aspects of metabolic disorders. Because of their ability to lower blood sugar, reduce weight, improve cardiovascular health, and preserve β cells, glucagon-like peptide-1 (GLP-1) receptor agonists have become a revolutionary class of drugs. Advances in peptide engineering, half-life extension technologies, receptor selectivity, and molecular stability have increased the therapeutic potential of GLP-1 analogs. In addition, the development of dual and triple incretin agonists, small molecule GLP-1 agonists and synergistic metabolic targets such as GIP, glucagon, AMPK and FGFR1C have enabled new treatment pathways for complex metabolic diseases. This review examines the design, optimization, and clinical use of GLP-1 analogs and next-generation incretin-baseddrugs, highlighting new developments,challenges, and opportunities for metabolic drug development.