Abstract
Diabetes mellitus affects over 530 million adults globally, with current therapies limited by frequent dosing, <20% oral bioavailability, and poor long-term glycemic control. Nanomedicine, particularly self-assembled peptide nanostructures (nanofibrils), offers sustained, glucose-responsive drug release and extended peptide bioactivity for several days per dose. This review critically evaluates recent advances in smart antidiabetic nanomedicine, focusing on quantitative improvements in pharmacokinetics, controlled release, and patient compliance compared with conventional treatments. It also outlines remaining challenges in large-scale synthesis, safety validation, and regulatory translation. Collectively, these insights highlight the potential of reversible peptide nanofibrils as long-acting, cost-effective therapeutics for improved diabetes management.