A comprehensive review on DPP-4 inhibitory small bioactive peptides in type −2 diabetes mellitus management

ABSTRACT Diabetes Mellitus Type 2 diabetes (T2DM) remains a significant health issue in the world, characterized by insulin resistance and glucose metabolic dysfunction. In this regard, the dipeptidyl peptidase-4 (DPP-4) inhibitors, which are the therapeutic strategy of interest applicable in maintaining the functionality of incretin hormones in the control of postprandial glucose levels. Recently, small peptides have received attention as DPP-4 inhibitors as they are small peptides have specificity, low toxicity, and are biodegradable. Molecular docking, virtual screening and machine learning enabled in silico approaches have greatly reduced the search space of DPP-4 inhibitory peptides. This review identifies the structural aspects of DPP-4, mechanisms of peptide-based inhibition, and discusses the current advances in the use of computational tools in peptide discovery. Small peptides are found to have great potential to overcome the problems associated with existing inhibitors, and offer exciting opportunities in the development of new diabetes management approaches. Future work should consist of improving peptide stability and determining their possible clinical applications.