Dipeptidyl peptidase-4 Inhibitors in Type 2 Diabetes Mellitus: Mechanisms and Efficacy in Clinical Practice

Abstract

Type 2 diabetes mellitus (T2DM) is a long-term metabolic condition marked by reduced insulin release, decreased sensitivity to insulin, and hyperglucagonemia. In recent years, dipeptidyl peptidase-4 (DPP-4) inhibitors have become increasingly significant within the newer classes of antidiabetic medications, thanks to their distinct mechanism of action, advantageous safety profile, and the convenience of oral administration. In contrast to sulfonylureas, which have a significant risk of causing hypoglycemia, DPP-4 inhibitors offer insulin stimulation that depends on glucose levels, making them a safer choice for many patients. The aim of this study is to investigate the mechanisms and efficacy of DPP-4 inhibitors in clinical practice. The incretin effects of DPP-4 inhibitors are mediated by the hormone glucagon-like peptide-1 (GLP-1) and glucose- dependent insulinotropic polypeptide (GIP). GLP-1 and GIP stimulates insulin secretion. Furthermore, DPP-4 inhibitors hinder apoptosis in cells. For example, suppressing apoptosis in cardiac, renal, and pancreatic beta cells may be advantageous for enhancing insulin secretion and minimizing complications related to diabetes. DPP-4 inhibitors reduce inflammatory cytokines and chemokines by inhibiting nuclear factor kappa-light- chain-enhancer of activated B cells (NF-κB). In addition, they mitigate inflammation through modulation of immune cell activity and upregulation of anti-inflammatory chemokines and adipokines. Also, DPP-4 inhibitors have antioxidant roles, such as improving antioxidant factors and downregulating oxidant agents. Considering that T2DM is characterized as an inflammatory disease, DPP-4 inhibitors elevate insulin secretion and sensitivity, improve glycemic indices, and mitigate diabetic complications through incretin, anti- inflammatory, and antioxidant effects