Advances in GLP-1 receptor agonists delivery systems for obesity and diabetes

Obesity and diabetes are chronic metabolic diseases affecting millions worldwide. Current treatments, including lifestyle changes, medications, and surgery, face challenges like poor adherence and side effects. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended innovative medications for these conditions, with studies showing significant clinical benefits. GLP-1RAs are traditionally delivered orally or via subcutaneous injections, but these methods have limitations, including low bioavailability, poor solubility, the need for high doses, gastrointestinal side effects, and frequent dosing requirements. Novel delivery technologies offer promising strategies to overcome these challenges and enhance therapeutic effectiveness. Recent advances in drug delivery technologies, including nanocarrier- and microcarrier-based systems, hydrogels, microneedles, and innovative formulations such as long-acting, co- and/or nano-formulated agents, offer promising strategies to enhance the delivery, efficacy, and patient adherence of GLP-1RAs for obesity and diabetes. This review focuses on innovative delivery technologies developed for three main GLP-1RAs: exenatide, liraglutide, and semaglutide. We present a review of advancements in drug delivery systems, exploring technologies employed in the development of these agents, as well as future challenges. It is crucial to note that these technologies are still in early development, and further studies are needed to confirm their long-term safety, efficacy, and cost-effectiveness in clinical use.