Sitagliptin CAS NO 654671-78-0 Inquire about Sitagliptin

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What is Sitagliptin Base?

Sitagliptin base (INN; previously identified as MK-0431 and marketed as the phosphate salt under the trade name Januvia) is an oral antihyperglycemic (antidiabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It was developed, and is marketed, by Merck & Co. This enzyme-inhibiting drug is used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a thiazolidinedione) for treatment of diabetes mellitus type 2. The benefit of this medicine is its fewer side effects (e.g., less hypoglycemia, less weight gain) in the control of blood glucose values. While safety is its advantage, efficacy is often challenged as it is often recommended to be combined with other agents like metformin.

Indication

Sitagliptin Base is used as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Sitagliptin Base is also used in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin or a PPAR¦Ã agonist (e.g., thiazolidinediones) when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Pharmacodynamics

Sitagliptin base 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.

What is the 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.

What are the side effects of Sitagliptin Base?

In clinical trials, adverse effects were as common with sitagliptin (whether used alone or with metformin or pioglitazone) as they were with placebo, except for extremely rare nausea and common cold-like symptoms. There is no significant difference in the occurrence of hypoglycemia between placebo and sitagliptin.

There have been several postmarketing reports of pancreatitis (some fatal) in people treated with sitagliptin, and the U.S. package insert carries a warning to this effect, although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated.

How to dose Sitagliptin Base?

The recommended dose of Sitagliptin Base is 100 mg once daily. Sitagliptin Base can be taken with or without food.

Patients with Renal Insufficiency:

For patients with mild renal insufficiency (creatinine clearance [CrCl] greater than or equal to 50 mL/min, approximately corresponding to serum creatinine levels of less than or equal to 1.7 mg/dL in men and less than or equal to 1.5 mg/dL in women), no dosage adjustment for Sitagliptin Base is required.

For patients with moderate renal insufficiency (CrCl greater than or equal to 30 to less than 50 mL/min, approximately corresponding to serum creatinine levels of greater than 1.7 to less than or equal to 3.0 mg/dL in men and greater than 1.5 to less than or equal to 2.5 mg/dL in women), the dose of Sitagliptin Base is 50 mg once daily.

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.