Advancements in in vitro simulated digestion-derived peptides for type 2 diabetes mellitus management: From therapeutic challenges to dietary opportunities.

Type 2 diabetes mellitus (T2DM) is a growing global health concern, with significant economic implications. Bioactive peptides (BAPs) produced by in vitro simulated digestion (IVSD) can be safe and cost-effective alternatives to pharmacological treatments. These peptides act holistically by inhibiting key enzymes, enhancing insulin sensitivity, and restoring β-cell functions. Although the efficacy of IVSD-derived peptides has been validated through in vitro, in vivo, and in silico assays, translating these findings into therapeutic medicine faces several challenges, from limited clinical trial data to scaling up the peptide-synthesis process. Despite these obstacles, IVSD-derived peptides offer opportunities for functional food formulation and nutraceutical development for T2DM regulation. This review focuses on developing innovative strategies to incorporate these peptides into dietary interventions for managing T2DM. By addressing these knowledge gaps and challenges, the transition of IVSD-derived BAPs from laboratory discoveries to industrial and therapeutic applications offers a promising approach for managing T2DM.