What is the mechanism of Sitagliptin?

Sitagliptin is an oral antihyperglycemic agent that is used in the management of type 2 diabetes mellitus. Its primary mechanism of action revolves around the inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4). To understand how sitagliptin works, it is essential to delve into the role of incretin hormones in the regulation of glucose metabolism.

Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the gut in response to food intake. These hormones play a crucial role in maintaining glucose homeostasis. They enhance the secretion of insulin from pancreatic beta cells in a glucose-dependent manner and inhibit the release of glucagon from pancreatic alpha cells, which in turn reduces hepatic glucose production.

However, the activity of incretin hormones is short-lived because they are rapidly degraded by the enzyme DPP-4. This is where sitagliptin comes into play. Sitagliptin is a potent, selective DPP-4 inhibitor. By inhibiting DPP-4, sitagliptin increases the levels of active incretin hormones. This prolongation of incretin activity leads to enhanced insulin secretion and decreased glucagon release in response to meals, thereby improving glycemic control.

The improved insulin secretion helps in lowering postprandial glucose levels (blood sugar levels after eating), while the reduced glucagon levels help in lowering fasting glucose levels. These dual effects contribute to overall better management of blood glucose levels in individuals with type 2 diabetes.

Sitagliptin is generally well-tolerated, with a low risk of hypoglycemia when used alone, as its mechanism of action is glucose-dependent. This means that it primarily enhances insulin secretion only when blood glucose levels are elevated, minimizing the risk of blood sugar dropping too low.

In addition to its efficacy in controlling blood glucose levels, sitagliptin is usually administered once daily, which can improve patient adherence to the medication regimen. It can be used as monotherapy or in combination with other antihyperglycemic agents, such as metformin, sulfonylureas, or thiazolidinediones, to achieve better glycemic control.

In summary, sitagliptin aids in the management of type 2 diabetes mellitus through the inhibition of the DPP-4 enzyme, resulting in increased levels of active incretin hormones. This leads to enhanced insulin secretion and reduced glucagon release, which together help in maintaining better blood glucose levels. Its glucose-dependent mechanism of action minimizes the risk of hypoglycemia, making it a valuable option in the therapeutic arsenal against type 2 diabetes.