Comprehensive Monograph on Sitagliptin (DB01261)

Introduction and Physicochemical Profile

Overview and Drug Classification

Sitagliptin is an oral, once-daily, highly selective small molecule inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme.[1] As the first-in-class therapeutic agent in this category, its approval marked a significant advancement in the management of type 2 diabetes mellitus (T2DM) by introducing a novel mechanism of action centered on the enhancement of the endogenous incretin system.[1] Developed by Merck & Co., sitagliptin offers a distinct approach to glycemic control, characterized by a favorable profile with respect to hypoglycemia and weight neutrality when used as monotherapy, which contrasts with many older classes of antidiabetic agents.[1] It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.[3]

The drug works by increasing the production of insulin and decreasing the production of glucagon by the pancreas in a glucose-dependent manner.[1] This targeted physiological modulation allows for effective lowering of both fasting and postprandial glucose levels. Sitagliptin is available as a single-agent therapy and in fixed-dose combinations with other widely used antidiabetic medications, reflecting its versatility in multidrug regimens for a chronic, progressive disease.[1]

Chemical Identity and Physicochemical Properties