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Sitagliptin is an oral diabetes medicine that helps control blood sugar levels. It works by regulating the levels of insulin your body produces after eating. Sitagliptin is for people with type 2 diabetes. It is sometimes used in combination with other diabetes medications, but is not for treating type 1 diabetes.

Active ingredient:
Brand Name: Januvia
Incorrect generic name: Sitagliptin Phosphate
Categories: diabetes

Synonym(s): MK-0431, Sitagliptan, Sitagliptina, Sitagliptine, Sitagliptinum, Sitagliptin phosphate
It is also sold under the brand name(s): Januvia, Janumet XR

Sitagliptin is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. This enzyme-inhibiting drug is to be used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. The drug works to competitively inhibit a protein/enzyme, dipeptidyl peptidase 4 (DPP-4), that results in an increased amount of active incretins (GLP-1 and GIP), reduced amount of release of glucagon (diminishes its release) and increased release of insulin.


For use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Also for use in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin or a PPARĪ³ agonist (e.g., thiazolidinediones) when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Mechanism of action

Sitagliptin is a highly selective DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones, thereby increasing the concentration and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. These changes lead to a decrease in hemoglobin A1c (HbA1c)levels, as well as a lower fasting and postprandial glucose concentration. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.


Sitagliptin is an orally-active member of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. The benefit of this medicine is expected to be its lower side-effects of hypoglycemia in the control of blood glucose values. The drug works to diminish the effects of a protein/enzyme (by the inhibition of this protein/enzyme) on the pancreas at the level of release of glucagon (diminishes its release) and at the level of insulin (increases its synthesis and release) until blood glucose levels are restored toward normal, in which case the protein/enzyme-enzyme inhibitor becomes less effective and the amounts of insulin released diminishes thus diminishing the “overshoot” of hypoglycemia seen in other oral hypoglycemic agents.


Sitagliptin does not undergo extensive metabolism. In vitro studies indicate that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4 (oxidation), with contribution from CYP2C8.


Rapidly absorbed following oral administration, with an absolute bioavailability of 87%.

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