A review of recent research and development on GLP-1 receptor agonists-sustained-release microspheres

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.