Designing GLP-1 delivery: structural perspectives and formulation approaches for optimized therapy

GLP-1 and its synthetic analogs have emerged as significant therapeutic agents for the management of metabolic disorders, merging glycemic control with weight loss through innovative structural and delivery breakthroughs. This review provides a meticulous exploration of GLP-1, elucidating its origin, secretion, and the challenges associated with its clinical application due to its fragility in the presence of DPP-IV, resulting in a short half-life. To overcome this limitation, various modifications and delivery strategies to enhance the pharmacokinetic properties and therapeutic efficacy of GLP-1 analogs have been studied. The review delves into the intricacies of different modification approaches, including N and C-terminal modifications, Fatty acid Side chain Modifications, and Large Molecule Conjugation Modifications, highlighting their rationale and resulting improvements in half-life, stability, receptor binding, and bioactivity. Additionally, the importance of optimized delivery strategies to ensure sustained and controlled release of GLP-1 analogs is discussed. The culmination of these scientific advancements provides valuable insights for the development of more effective treatments for metabolic disorders, ultimately paving the way for improved patient outcomes in the realm of metabolic health.