Review identifies novel strategies to boost oral semaglutide bioavailability by overcoming GI barriers

Oral semaglutide, a GLP-1 Receptor Agonist, offers a convenient option for type 2 diabetes mellitus and obesity management. However, its oral bioavailability is exceedingly low due to significant gastrointestinal and biopharmaceutical barriers. These include instability in acidic GI fluids, rapid degradation by proteolytic enzymes, limited diffusion through the mucus layer, and poor epithelial permeability. Overcoming these challenges is crucial for maximizing the therapeutic potential and patient accessibility of oral semaglutide, addressing a key gap in current delivery methods.

This review systematically identified and summarized methods to enhance oral bioavailability and treatment efficacy of semaglutide. Researchers searched databases including Scopus, Google Scholar, PubMed, and clinicaltrials.gov to gather information on various formulation strategies. The scope encompassed work on enteric coating, gut-targeted delivery, and other approaches designed to improve oral absorption. The review also discussed and summarized all relevant patents and clinical trials related to advanced semaglutide formulations, providing a broad perspective on current and emerging delivery technologies.

The review highlighted that current oral semaglutide formulations face severe limitations due to instability in gastric acid and extensive enzymatic degradation, leading to exceedingly low oral bioavailability. It identified enteric coating as a primary strategy to protect the drug from acidic degradation in the stomach, ensuring its intact delivery to the intestine. Furthermore, gut-targeted delivery approaches were emphasized to facilitate localized release and absorption in the intestinal tract, bypassing early GI barriers. The review also detailed strategies aimed at preventing proteolysis by various digestive enzymes and enhancing epithelial permeability to improve the drug's uptake across the intestinal lining. These combined formulation strategies are proposed to significantly increase the overall oral absorption of semaglutide. The analysis also covered existing patents and clinical trials for these advanced formulations, underscoring active research and development in this critical area. > The expert opinion proposes novel and promising strategies for gut-targeted delivery and enteric coating to prevent acidic degradation and enzymatic breakdown, thereby enhancing intestinal uptake.