Sitagliptin: Difference between revisions
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{{Short description|Diabetes medication}} | {{Short description|Diabetes medication}} | ||
{{Infobox drug | {{Infobox drug | ||
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| pronounce = {{IPAc-en|audio=En-us-Sitagliptin.ogg|s|ɪ|t|ə|ˈ|g|l|ɪ|p|t|ɪ|n}} | | pronounce = {{IPAc-en|audio=En-us-Sitagliptin.ogg|s|ɪ|t|ə|ˈ|g|l|ɪ|p|t|ɪ|n}} | ||
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| ATC_supplemental = | | ATC_supplemental = | ||
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| legal_status = <!-- For countries not listed above --> | | legal_status = <!-- For countries not listed above --> | ||
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| bioavailability = 87% | | bioavailability = 87% | ||
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| excretion = [[Kidney]] (80%) | | excretion = [[Kidney]] (80%) | ||
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| IUPAC_name = (''R'')-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-''a'']pyrazin-7(8''H'')-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine | | IUPAC_name = (''R'')-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-''a'']pyrazin-7(8''H'')-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine | ||
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<!-- Definition and medical uses --> | <!-- Definition and medical uses --> | ||
'''Sitagliptin''', sold under the brand name '''Januvia''' among others, is an [[anti-diabetic medication]] used to treat [[type 2 diabetes]]. In the United Kingdom it is listed as less preferred than [[metformin]] or a [[sulfonylurea]]. It is taken [[Oral administration|by mouth]]. It is also available in the [[fixed-dose combination]] medication [[sitagliptin/metformin]] (Janumet, Janumet XR). | '''Sitagliptin''', sold under the brand name '''Januvia''' among others, is an [[anti-diabetic medication]] used to treat [[type 2 diabetes]]. In the United Kingdom it is listed as less preferred than [[metformin]] or a [[sulfonylurea]]. It is taken [[Oral administration|by mouth]]. It is also available in the [[fixed-dose combination]] medication [[sitagliptin/metformin]] (Janumet, Janumet XR). | ||
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<!-- Side effects and mechanisms --> | <!-- Side effects and mechanisms --> | ||
Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]]. Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas. | Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]]. Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas. | ||
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<!-- Society and culture --> | <!-- Society and culture --> | ||
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{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States. | 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{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States. | ||
==Medical uses== | ==Medical uses== <!--T:10--> | ||
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 combination]]s of [[sitagliptin/metformin]] (Janumet, Janumet XR) and [[sitagliptin/simvastatin]] (Juvisync). | 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 combination]]s of [[sitagliptin/metformin]] (Janumet, Janumet XR) and [[sitagliptin/simvastatin]] (Juvisync). | ||
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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. | 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== <!--T:12--> | ||
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 [[statistical significance|significant]] difference exists in the occurrence of [[hypoglycemia]] between placebo and sitagliptin. In those taking [[sulphonylurea]]s, the risk of [[hypoglycemia|low blood sugar]] is increased. | 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 [[statistical significance|significant]] difference exists in the occurrence of [[hypoglycemia]] between placebo and sitagliptin. In those taking [[sulphonylurea]]s, the risk of [[hypoglycemia|low blood sugar]] is increased. | ||
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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. | 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. | ||
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Several [[postmarketing surveillance|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. | Several [[postmarketing surveillance|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. | ||
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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. | 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== | ==Mechanism of action== <!--T:16--> | ||
{{see also|Dipeptidyl peptidase-4 inhibitors}} | {{see also|Dipeptidyl peptidase-4 inhibitors}} | ||
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Sitagliptin works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s 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 works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s 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. | ||
<!--T:18--> | |||
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. | 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. | ||
==History== | ==History== <!--T:19--> | ||
{{see also|Development of dipeptidyl peptidase-4 inhibitors}} | {{see also|Development of dipeptidyl peptidase-4 inhibitors}} | ||
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Sitagliptin was approved by the U.S. [[Food and Drug Administration]] (FDA) in October 2006, and is marketed in the US as Januvia by [[Merck & Co.]] On April 2, 2007, the FDA approved an oral combination of [[sitagliptin/metformin]] sold in the US under the brand name Janumet. On October 7, 2011, the FDA approved an oral combination of [[sitagliptin/simvastatin]] marketed in the US as Juvisync. | Sitagliptin was approved by the U.S. [[Food and Drug Administration]] (FDA) in October 2006, and is marketed in the US as Januvia by [[Merck & Co.]] On April 2, 2007, the FDA approved an oral combination of [[sitagliptin/metformin]] sold in the US under the brand name Janumet. On October 7, 2011, the FDA approved an oral combination of [[sitagliptin/simvastatin]] marketed in the US as Juvisync. | ||
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{{-}} | {{-}} | ||
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{{Oral hypoglycemics}} | {{Oral hypoglycemics}} | ||
{{Merck&Co}} | {{Merck&Co}} | ||
{{Portal bar | Medicine}} | {{Portal bar | Medicine}} | ||
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{{二次利用|date=4 February 2024}} | {{二次利用|date=4 February 2024}} | ||
[[Category:Wikipedia medicine articles ready to translate]] | [[Category:Wikipedia medicine articles ready to translate]] | ||
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[[Category:Triazoles]] | [[Category:Triazoles]] | ||
[[Category:Drugs developed by Merck & Co.]] | [[Category:Drugs developed by Merck & Co.]] | ||
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Latest revision as of 20:17, 12 March 2024
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| Clinical data | |
|---|---|
| Pronunciation | /sɪtəˈɡlɪptɪn/ ( listen) |
| Trade names | Januvia, Zituvio, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a606023 |
| License data |
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| Pregnancy category |
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| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 87% |
| Protein binding | 38% |
| Metabolism | Liver (CYP3A4- and CYP2C8-mediated) |
| Elimination half-life | 8 to 14 h |
| Excretion | Kidney (80%) |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C16H15F6N5O |
| Molar mass | 407.320 g·mol−1 |
| 3D model (JSmol) | |
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| (verify) | |
Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin (Janumet, Janumet XR).
Common side effects include headaches, swelling of the legs, and upper respiratory tract infections. Serious side effects may include angioedema, low blood sugar, kidney problems, pancreatitis, and joint pain. Whether use in pregnancy or breastfeeding is safe is unclear. It is in the dipeptidyl peptidase-4 (DPP-4) inhibitor class and works by increasing the production of insulin and decreasing the production of glucagon by the pancreas.
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
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.
History
Sitagliptin was approved by the U.S. Food and Drug Administration (FDA) in October 2006, and is marketed in the US as Januvia by Merck & Co. On April 2, 2007, the FDA approved an oral combination of sitagliptin/metformin sold in the US under the brand name Janumet. On October 7, 2011, the FDA approved an oral combination of sitagliptin/simvastatin marketed in the US as Juvisync.
 | この記事は、クリエイティブ・コモンズ・表示・継承ライセンス3.0のもとで公表されたウィキペディアの項目Sitagliptin(4 February 2024編集記事参照)を素材として二次利用しています。 Item:Q21469  |