Incretin-Based Therapies Through the Decades: Molecular Innovations and Clinical Impact

The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice.