Current trends in semaglutide therapy and strategies to improve its bioavailability

INTRODUCTION: A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. AREAS COVERED: This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. EXPERT OPINION: Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake.