DIPEPTIDYL PEPTIDASE-4 (DPP4) IN DIABETES MELLITUS: MOLECULAR MECHANISMS, PATHOPHYSIOLOGICAL SIGNIFICANCE, THERAPEUTIC APPLICATIONS AND EMERGING PERSPECTIVES

Diabetes mellitus is a major metabolic disorder characterised by chronic hyperglycaemia resulting from impaired insulin secretion, insulin action or both, leading to progressive systemic complications. Dipeptidyl peptidase-4 (DPP4/CD26) has emerged as a key regulator of glucose homeostasis through the degradation of incretin hormones, particularly glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thereby influencing insulin secretion and glucagon regulation. This review aimed to comprehensively evaluate the molecular biology, physiological functions, pathological roles and therapeutic significance of DPP4 in diabetes mellitus. Relevant literature was retrieved from PubMed, Scopus, Web of Science and Google Scholar, with emphasis on peer-reviewed experimental studies, clinical investigations and recent review articles. The available evidence demonstrates that DPP4 contributes not only to impaired incretin activity but also to insulin resistance, β-cell dysfunction, chronic inflammation, oxidative stress and the development of diabetic complications, including nephropathy, retinopathy, neuropathy, cardiovascular disease and metabolic dysfunction-associated fatty liver disease. Clinically, DPP4 inhibitors have become an established class of oral antidiabetic agents with favourable efficacy and safety profiles, while emerging evidence suggests additional anti-inflammatory and tissue-protective effects. Latest investigations also highlight the potential involvement of DPP4 in immunometabolism, gut microbiota interactions, extracellular vesicle signalling and precision medicine; however, these applications require further clinical validation. Overall, DPP4 represents a central therapeutic target in diabetes mellitus and continues to provide important opportunities for improving disease management and guiding future translational research.