Sitagliptin/ja

Sitagliptin/ja

Clinical data
Pronunciation	/sɪtəˈɡlɪptɪn/ (listen)
Trade names	Januvia, Zituvio, others
AHFS/Drugs.com	Monograph
MedlinePlus	a606023
License data	US DailyMed: Sitagliptin
Pregnancy category	AU: B3
Routes of administration	経口
ATC code	A10BH01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only EU: Rx-only
Pharmacokinetic data
Bioavailability	87%
Protein binding	38%
Metabolism	肝臓 (CYP3A4- と CYP2C8-介在)
Elimination half-life	8 to 14 h
Excretion	Kidney/ja (80%)
Identifiers
IUPAC name (R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine
CAS Number	486460-32-6 Y
PubChem CID	4369359
IUPHAR/BPS	6286
DrugBank	DB01261 Y
ChemSpider	3571948 Y
UNII	QFP0P1DV7Z
KEGG	D08516 as salt: D06645
ChEBI	CHEBI:40237 Y
ChEMBL	ChEMBL1422 Y
Chemical and physical data
Formula	C16H15F6N5O
Molar mass	407.320 g·mol−1
3D model (JSmol)	Interactive image
SMILES Fc1cc(c(F)cc1F)C[C@@H](N)CC(=O)N3Cc2nnc(n2CC3)C(F)(F)F
InChI InChI=1S/C16H15F6N5O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22/h4,6,9H,1-3,5,7,23H2/t9-/m1/s1 Y Key:MFFMDFFZMYYVKS-SECBINFHSA-N Y
(verify)

シタグリプチン（sitagliptin, ブランド名ジャヌビア他）は、2型糖尿病の治療に用いられる抗糖尿病薬である。イギリスではメトホルミンやスルホニルウレアよりも優先度が低いとされている。口から服用する。また、合剤医薬品シタグリプチン/メトホルミン（ジャヌメット、ジャヌメットXR）もある。

一般的な副作用には、頭痛、脚の腫れ、上気道感染症などがある。重篤な副作用には、血管浮腫、低血糖、腎障害、膵炎、関節痛などがある。妊娠中や授乳中の使用が安全かどうかは不明である。ジペプチジルペプチダーゼ-4（DPP-4）阻害薬クラスに属し、膵臓によるインスリンの産生を増加させ、グルカゴンの産生を減少させることで作用する。

Sitagliptin was developed by Merck & Co. and approved for medical use in the United States in 2006. In 2021, it was the 83rd most commonly prescribed medication in the United States, with more than 8 million prescriptions. It is available as a generic medication in Canada but not the United States.

Medical uses

Sitagliptin is used to treat type 2 diabetes. It is generally less preferred than metformin or sulfonylureas. It is taken by mouth. It is also available as the fixed-dose combinations of sitagliptin/metformin (Janumet, Janumet XR) and sitagliptin/simvastatin (Juvisync).

Sitagliptin should not be used to treat type 1 diabetes. In December 2020, the U.S. Food and Drug Administration (FDA) approved labeling changes stating that Januvia (sitagliptin), Janumet (sitagliptin and metformin hydrochloride), and Janumet XR (sitagliptin and metformin hydrochloride extended-release) are not proven to improve glycemic (blood sugar) control in children aged 10 to 17 with type 2 diabetes. The drugs are approved to improve blood sugar control in adults aged 18 and older with type 2 diabetes.

Adverse effects

Adverse effects from sitagliptin are similar to placebo, except for rare nausea, common cold-like symptoms, and photosensitivity. It does not increase the risk of diarrhea. No significant difference exists in the occurrence of hypoglycemia between placebo and sitagliptin. In those taking sulphonylureas, the risk of low blood sugar is increased.

The existence of rare case reports of kidney failure and hypersensitivity reactions is noted in the United States prescribing information, but a causative role for sitagliptin has not been established.

Several postmarketing reports of pancreatitis (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, 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. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors.

In 2015, the U.S. Food and Drug Administration (FDA) added a new warning and precaution about the risk of "severe and disabling" joint pain to the labels of all DPP-4 inhibitor medicines.

Mechanism of action

See also: Dipeptidyl peptidase-4 inhibitors

Sitagliptin works to competitively inhibit the enzyme dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the incretins GLP-1 and GIP, gastrointestinal hormones released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of 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.

Sitagliptin has been shown to lower HbA1c level by about 0.7% points versus placebo. It is slightly less effective than metformin when used as a monotherapy. It does not cause weight gain and has less hypoglycemia compared to sulfonylureas. Sitagliptin is recommended as a second-line drug (in combination with other drugs) after the combination of diet/exercise and metformin fails.

歴史

「Development of dipeptidyl peptidase-4 inhibitors/ja」も参照

シタグリプチンは2006年10月に米国食品医薬品局（FDA）によって承認され、米国ではMerck & Co.からジャヌビアとして販売されている。2007年4月2日、FDAはシタグリプチン/メトホルミンの経口配合剤を承認し、米国ではジャヌメットの商品名で販売されている。2011年10月7日、FDAは米国でJuvisyncとして販売されているシタグリプチン/シンバスタチンの経口配合剤を承認した。