Synthetic Overview of FDA-Approved Dipeptidyl Peptidase-4 Inhibitors (DPP-4I)

Diabetes mellitus continues to be a major health concern worldwide, contributing significantly to annual mortality and morbidity. Among all types of diabetes mellitus, type 2 diabetes mellitus is a pervasive health condition that affects people worldwide. Recently, various classes of drugs have been proposed for the management of T2DM. Dipeptidyl peptidase-4 inhibitors or gliptins are a class of oral medications for T2DM that target the incretin hormones GLP-1 and GIP. By increasing insulin production and decreasing glucagon release, DPP-4 inhibitors maintain glucose homeostasis. DPP-4 inhibitors provide a number of advantages over conventional antidiabetic medications, including a reduced risk of hypoglycaemic episodes, an extensive safety profile, and no weight gain. Consequently, gliptins have been a focus of study. This paper provides an overview of diabetes mellitus, focusing on its types, prevalence, and therapeutic approaches, particularly in the context of type 2 diabetes mellitus (T2DM). The synthesis of key DPP-4 inhibitors, including sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin is discussed, showcasing various synthetic strategies employed by different researchers to produce these drugs.