Oral Delivery Challenges & Formulation Strategies for Glucagon Like Peptide-1 Receptor Agonists

Glucagon-like peptide-1 receptor agonists are highly effective therapeutic agents for the management of type 2 diabetes mellitus & obesity due their glucose-dependent insulinotropic activity, appetite suppression, & cardiometabolic benefits. However, their clinical use has traditionally been limited injectable formulations because of poor oral bioavailability resulting from enzymatic degradation, acidic gastric conditions, low intestinal permeability, & extensive first-pass metabolism. The development of orally administered glucagon like peptide-1 receptor agonists represents a major advancement in peptide drug delivery but remains scientifically challenging. Biological/physicochemical barriers to oral delivery of GLP-1 and innovative formulation strategies designed to overcome these obstacles, including absorption enhancers, enzyme inhibitors, nanocarriers, gastroretentive formulations and multi-mechanistic delivery systems are critically reviewed in this article. Furthermore, safety concerns, regulatory aspects and future perspectives for the oral preparation of glucagon-like peptide-1 receptor agonists are discussed emphasizing the importance to develop creative as well as patient-friendly administration forms.