Introduction: Αlpha-Glucosidase Inhibitors (AGIs) are a class of oral antidiabetic agents that effectively control postprandial hyperglycemia by delaying carbohydrate digestion and absorption in the small intestine through the inhibition of the α-glucosidase enzyme, representing a therapeutic strategy to manage postprandial hyperglycemia in Type 2 Diabetes Mellitus (T2DM). Although synthetic AGIs such as acarbose are clinically effective, their use is often limited by gastrointestinal side effects. Methods: A systematic literature search was performed across PubMed, ScienceDirect, and Google Scholar for studies published between 2000 and 2025. Keywords included “α-glucosidase inhibitors,” “natural compounds,” “flavonoids,” “tannins,” “xanthones,” “coumarins,” “sugar mimics,” and “marine-derived compounds.” Peer-reviewed original research and review articles in English were included, while conference abstracts, unpublished data, and non-peer-reviewed literature were excluded. Results: Natural AGIs, including flavonoids, xanthones, tannins, coumarins, sugar mimics, and marine bromophenols, provide structurally diverse scaffolds with significant α-glucosidase inhibitory activity. These compounds exhibit competitive, non-competitive, or mixed-type inhibition depending on their structure and experimental conditions. Despite promising in vitro results, most natural AGIs face challenges such as poor bioavailability, metabolic instability, and limited clinical validation. Discussion: Natural AGIs derived from diverse natural compounds demonstrate promising potential for managing postprandial hyperglycemia in T2DM, although their clinical application remains limited due to challenges related to bioavailability and insufficient clinical validation. Conclusion: Natural α-glucosidase inhibitors represent a potentially safer alternative to synthetic drugs for postprandial hyperglycemia management. Comprehensive in vivo pharmacokinetic and toxicity studies, along with mechanistic investigations and clinical trials, are necessary to evaluate their therapeutic potential in T2DM.
Perveen et al. (Fri,) studied this question.