Sitagliptin

drugbox

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IUPAC_name = (3"R")-3-amino-1- [9-(trifluoromethyl)-
1,4,7,8-tetrazabicyclo [4.3.0] nona-6,8-d ien-4-yl] -
4-(2,4,5-trifluorophenyl)butan-1-one
width=254
CAS_number = 790712-60-6
ATC_prefix = A10
ATC_suffix = BH01
PubChem = 4369359
DrugBank =
C = 16 |H = 15 |N = 5 |O = 1 |F = 6
molecular_weight = 407.314 g/mol
bioavailability = 87%
protein_bound = 38%
metabolism = Hepatic (CYP3A4- and CYP2C8-mediated)
elimination_half-life = 8 to 14 hourscite journal | author = Herman G, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang A, Zeng W, Musson D, Winchell G, Davies M, Ramael S, Gottesdiener K, Wagner J | title = Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. | journal = Clin Pharmacol Ther | volume = 78 | issue = 6 | pages = 675–88 | year = 2005 | pmid = 16338283 | doi = 10.1016/j.clpt.2005.09.002]
excretion = Renal (80%)
pregnancy_US = B
licence_EU = Januvia
licence_US = Sitagliptin
legal_UK = POM
legal_US = Rx-only
routes_of_administration = Oral

Sitagliptin (INN; previously identified as MK-0431, trade name Januvia) is an oral antihyperglycemic (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. 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 lower side-effects (e.g., less hypoglycemia, less weight gain) in the control of blood glucose values. Exenatide/Byetta is an alternative drug that also works with the incretin system.

Adverse effects

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 nausea and common cold-like symptoms, which were more common with sitagliptin.cite web | url = http://www.rxlist.com/cgi/generic/januvia_ad.htm | title = Januvia Side Effects & Drug Interactions | year = 2007 | accessdate = 2007-11-28 | publisher = RxList.com] There is no significant difference in the occurrence of hypoglycemia between placebo and sitagliptin.

History

Sitagliptin was approved by the U.S. Food and Drug Administration (FDA) on October 17, 2006cite press release
title = FDA Approves New Treatment for Diabetes
publisher = U.S. Food and Drug Administration
date = October 17, 2006
url = http://www.fda.gov/bbs/topics/NEWS/2006/NEW01492.html
accessdate = 2006-10-17 ] and is marketed in the US as Januvia by Merck & Co. On April 2, 2007, the FDA approved an oral combination of sitagliptin and metformin marketed in the US as Janumet.

Mechanism

Sitagliptin works to competitively inhibit the enzyme dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the incretins GLP-1 and GIP, gastrointestinal hormone that are released in response to a meal. [cite journal | author = Herman G, Bergman A, Liu F, Stevens C, Wang A, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan A, Lasseter K, Dilzer S, Blum R, Wagner J | title = Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. | journal = J Clin Pharmacol | volume = 46 | issue = 8 | pages = 876–86 | year = 2006 | pmid = 16855072 | doi = 10.1177/0091270006289850] By preventing GLP-1 and GIP inactivation, GLP-1 and GIP are able to potentiate the secretion of insulin and suppress the release of glucagon by the pancreas. This drives blood glucose levels towards normal. As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia) which is seen with some other oral hypoglycemic agents.

ee also

*Dipeptidyl peptidase-4

References

External links

* [http://www.januvia.com/ Official website]
* [http://www.merck.com/newsroom/press_releases/research_and_development/2006_0215.html Merck Announces FDA Acceptance of New Drug Application for JANUVIA] - Merck press release.
* [http://www.forbes.com/2004/01/26/cx_mh_rl_diabetestearsheet_5.html The race to get DPP-4 inhibitors to market] - Forbes.com
* [http://www.forbes.com/finance/2007/03/02/merck-novartis-januvia-pf-ii-in_dk_0302soapbox_inl.html Merck's March Madness] - Forbes.com
* - Sitagliptin
* - About DPP-4