Alogliptin: Difference between revisions

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{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = ~~437181578~~

| verifiedrevid = 454952697

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| IUPAC_name = 2-({6-[(3''R'')-3-~~aminopiperidin~~-1-yl]-3-methyl-2,4-dioxo-~~<br>~~3,4-dihydropyrimidin-1(2''H'')-yl}methyl)benzonitrile

| image = Alogliptin.svg

| alt =

| ~~tradename~~ =

| pronounce =

| tradename = Nesina, Vipidia<br />Kazano, Vipidomet (with [[metformin]])<br />Oseni, Incresync (with [[pioglitazone]])

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| pregnancy_AU = ~~~~

| Drugs.com = {{drugs.com|monograph|alogliptin}}

| pregnancy_US =

| MedlinePlus = a613026

| licence_EU = yes

| DailyMedID = Alogliptin

| licence_US =

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| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_US = B

| pregnancy_US_comment =

| pregnancy_category =

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| routes_of_administration = [[Oral administration|By mouth]]

| legal_AU =

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| ATC_prefix = A10

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| ATC_suffix = BH04

| legal_AU = S4

| legal_CA =

| legal_UK =

| legal_US = ~~~~

| legal_US = Rx-only

| ~~legal_status~~ =

| legal_EU = Rx-only

| legal_status = Rx-only

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| routes_of_administration = Oral

| bioavailability =

| bioavailability = 100%

| protein_bound =

| protein_bound = 20%

| metabolism =

| metabolism = Limited, [[liver]] ([[CYP2D6]]- and [[CYP3A4|3A4]]-mediated)

| elimination_half-life =

| elimination_half-life = 12–21 hours

| excretion =

| excretion = [[Kidney]] (major)<ref name=AACE/> and fecal (minor)

| IUPHAR_ligand = 6319

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| CAS_number = 850649-62-6

| CAS_number_Ref = {{cascite|correct|CAS}}

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| ATC_prefix = A10

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| CAS_number = 850649-61-5

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| ATC_suffix = BH04

| PubChem = 11450633

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 72323

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = JHC049LO86

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| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 376359

| synonyms = SYR-322

| index2_label = benzoate

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 850649-62-6

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = EEN99869SC

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| IUPAC_name = 2-({6-[(3''R'')-3-Aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2''H'')-yl}methyl)benzonitrile

| C=18 | H=21 | N=5 | O=2

| molecular_weight = 339.39 g/mol

| smiles = N#Cc3ccccc3CN\1C(=O)N(C)C(=O)/C=C/1N2CCC[C@@H](N)C2

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 9625485

| InChI = 1/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

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| ~~InChIKey~~ = ZSBOMTDTBDDKMP-~~OAHLLOKOBG~~

| StdInChI = 1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = ZSBOMTDTBDDKMP-OAHLLOKOSA-N

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| StdInChIKey = ZSBOMTDTBDDKMP-OAHLLOKOSA-N

}}

'''Alogliptin''' (codenamed '''SYR-322''') is an investigational [[anti-diabetic drug]] in the [[DPP-4 inhibitors|DPP-4 inhibitor]] class,<ref name="pmid17441705">{{cite journal |author=Feng J, Zhang Z, Wallace MB, ''et al.'' |title=Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV |journal=[[J. Med. Chem.]] |volume=50 |issue=10 |pages=2297–300 |year=2007 |pmid=17441705 |doi=10.1021/jm070104l}}</ref> being developed by [[Takeda Pharmaceutical Company]]. In January 2008, Takeda submitted a [[New Drug Application]] for alogliptin to the U.S. [[Food and Drug Administration]], after positive results from [[clinical trial#Phase III|Phase III]] [[clinical trial]]s.<ref>{{cite press release | url = http://www.takeda.com/press/article_28864.html | title = Takeda Submits New Drug Application for Alogliptin (SYR-322) in the U.S. | date = January 4, 2008 | accessdate = 2008-01-09 | publisher = [[Takeda Pharmaceutical Company]]}}</ref> However, the FDA submission was suspended or withdrawn in June 2009 needing more data.<ref>{{cite news|url=http://www.genengnews.com/news/bnitem.aspx?name=55661199&source=genwire|title=GEN News Highlights: Takeda Pulls MAA for Type 2 Diabetes Therapy|date=4 June 2009|publisher=Genetic Engineering and Biotechnology News}}</ref>

'''Alogliptin''', sold under the brand names '''Nesina''' and '''Vipidia''',<ref name=takedapr28864/><ref name=EMA2018>{{cite web |title=Vipidia |url=https://www.ema.europa.eu/documents/overview/vipidia-epar-summary-public_en.pdf |publisher=European Medicines Agency |access-date=31 March 2024 |archive-url=https://web.archive.org/web/20181101160452/https://www.ema.europa.eu/documents/overview/vipidia-epar-summary-public_en.pdf |archive-date=1 November 2018 |url-status=dead }}</ref> is an oral [[anti-diabetic drug]] in the [[Dipeptidyl peptidase-4 inhibitor|DPP-4 inhibitor]] (gliptin) class.<ref name=pmid17441705/> Like other members of the gliptin class, it causes little or no weight gain, exhibits relatively little risk of hypoglycemia, and has relatively modest glucose-lowering activity.<ref name=AACE/> Alogliptin and other gliptins are commonly used in combination with metformin in people whose diabetes cannot adequately be controlled with metformin alone.<ref name=AACE>{{cite web |url=https://www.aace.com/files/algorithm-07-11-2013.pdf |title=www.aace.com |archive-url=https://web.archive.org/web/20181101160532/https://www.aace.com/files/algorithm-07-11-2013.pdf |archive-date=2018-11-01 |url-status=dead }}</ref>

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==References==

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In April 2016, the U.S. [[Food and Drug Administration]] (FDA) added a warning about increased risk of [[heart failure]].<ref name=FDA2016>{{cite web|title= FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes |website=U.S. Food and Drug Administration (FDA) |access-date=16 March 2018 }}</ref> It was developed by Syrrx, a company which was acquired by [[Takeda Pharmaceutical Company]] in 2005.<ref>{{Cite web|url=http://www.utsandiego.com/uniontrib/20050208/news_1b8syrrx.html|title = The San Diego Union-Tribune - San Diego, California & National News}}</ref> In 2020, it was the 295th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022}}</ref><ref>{{cite web | title = Alogliptin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Alogliptin | access-date = 7 October 2022}}</ref>

==Medical uses==

Alogliptin is a [[dipeptidyl peptidase-4 inhibitor]] (DDP-4) that decreases blood sugar levels similar to other DPP-4 inhibitors.<ref>{{cite journal | vauthors = Saisho Y | title = Alogliptin benzoate for management of type 2 diabetes | journal = Vascular Health and Risk Management | volume = 11 | pages = 229–243 | date = 2015 | pmid = 25914541 | pmc = 4401208 | doi = 10.2147/VHRM.S68564 | doi-access = free }}</ref>

==Side effects==

Adverse events include [[hypoglycemia]],<ref name=seino2011/><ref name=kutoh2012/><ref name=bosi2011/> [[pruritis]] (itching),<ref name=EMA2018/> [[nasopharyngitis]], headache, and [[upper respiratory tract infection]].<ref name=FDA_Nesina/> It may also cause joint pain that can be severe and disabling.<ref>{{cite web|title=DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-dpp-4-inhibitors-type-2-diabetes-may-cause-severe-joint-pain|website=U.S. Food and Drug Administration (FDA)|access-date=1 September 2015|date=2015-08-28}}</ref> Like other DDP-4 inhibitors, alogliptin is weight-neutral.<ref name=AACE/>

A 2014 letter to the editor claimed alogliptin is not associated with increased risk of cardiovascular events.<ref>{{cite journal | vauthors = White WB, Zannad F | title = Saxagliptin, alogliptin, and cardiovascular outcomes | journal = The New England Journal of Medicine | volume = 370 | issue = 5 | pages = 484 | date = January 2014 | pmid = 24482824 | doi = 10.1056/NEJMc1313880 }}</ref>{{better source needed|reason=This is a letter to the editor.|date=March 2024}} In April 2016, the U.S. Food and Drug Administration (FDA) added a warning about increased risk of [[heart failure]].<ref name=FDA2016/>

==Market access==

[[File:Nesina Sales In China.jpg|thumb|Alogliptin tablets sales in mainland China. Specification is 25 mg × 10 tablets.]]

In December 2007, Takeda submitted a [[New Drug Application]] (NDA) for alogliptin to the [[Food and Drug Administration|United States Food and Drug Administration]] (FDA),<ref name=grogan2012/> after positive results from [[clinical trial#Phase III|Phase III clinical trials]].<ref name=takedapr28864/> In September 2008, the company also filed for approval in Japan,<ref name=geneng2009/> winning approval in April 2010.<ref name=grogan2012/> The company also filed a [[Marketing Authorization Application]] elsewhere outside the United States, which was withdrawn in June 2009 needing more data.<ref name=geneng2009/> The first NDA failed to gain approval and was followed by a pair of NDAs (one for alogliptin and a second for a combination of alogliptin and [[pioglitazone]]) in July 2011.<ref name=grogan2012/> In 2012, Takeda received a negative response from the FDA on both of these NDAs, citing a need for additional data.<ref name=grogan2012/>

In 2013, the FDA approved the drug in three formulations: as a stand-alone with the brand-name Nesina,<ref name="FDA_Nesina">{{cite web |title=Highlights of Prescribing Information: Nesina |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022271s000lbl.pdf |publisher=US Food and Drug Administration |access-date=31 March 2024}}</ref> combined with [[metformin]] using the name Kazano,<ref name="FDA_Kazano">{{cite web |title=Highlights of Prescribing Information: Kazano |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203414s000lbl.pdf |publisher=US Food and Drug Administration |access-date=31 March 2024}}</ref> and when combined with [[pioglitazone]] as Oseni.<ref name="FDA_Oseni">{{cite web |title=Highlights of Prescribing Information: Oseni |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022426s005lbl.pdf |publisher=US Food and Drug Administration |access-date=31 March 2024}}</ref>{{clear}}

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== References ==

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{{reflist|refs=

<ref name=geneng2009>{{cite news |url=http://www.genengnews.com/news/bnitem.aspx?name=55661199 |title=GEN News Highlights: Takeda Pulls MAA for Type 2 Diabetes Therapy |date=June 4, 2009 |publisher=[[Genetic Engineering & Biotechnology News]]}}</ref>

<ref name=grogan2012>{{Citation | vauthors = Grogan K |date=April 26, 2012 |title=FDA wants yet more data on Takeda diabetes drug alogliptin |periodical=[[PharmaTimes]] |at=PharmaTimes online | publisher=PharmaTimes |access-date=April 26, 2012 |url=http://www.pharmatimes.com/Article/12-04-26/FDA_wants_yet_more_data_on_Takeda_diabetes_drug_alogliptin.aspx }}</ref>

<ref name=pmid17441705>{{cite journal | vauthors = Feng J, Zhang Z, Wallace MB, Stafford JA, Kaldor SW, Kassel DB, Navre M, Shi L, Skene RJ, Asakawa T, Takeuchi K, Xu R, Webb DR, Gwaltney SL | display-authors = 6 | title = Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 10 | pages = 2297–2300 | date = May 2007 | pmid = 17441705 | doi = 10.1021/jm070104l }}</ref>

<ref name=seino2011>{{cite journal | vauthors = Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K | title = Efficacy and safety of alogliptin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, dose-ranging comparison with placebo, followed by a long-term extension study | journal = Current Medical Research and Opinion | volume = 27 | issue = 9 | pages = 1781–1792 | date = September 2011 | pmid = 21806314 | doi = 10.1185/03007995.2011.599371 | s2cid = 24082863 }}</ref>

<ref name=kutoh2012>{{cite journal | vauthors = Kutoh E, Ukai Y | title = Alogliptin as an initial therapy in patients with newly diagnosed, drug naïve type 2 diabetes: a randomized, control trial | journal = Endocrine | volume = 41 | issue = 3 | pages = 435–441 | date = June 2012 | pmid = 22249941 | doi = 10.1007/s12020-012-9596-0 | s2cid = 45948727 | publication-date = January 17, 2012 }}</ref>

<ref name=bosi2011>{{cite journal | vauthors = Bosi E, Ellis GC, Wilson CA, Fleck PR | title = Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study | journal = Diabetes, Obesity & Metabolism | volume = 13 | issue = 12 | pages = 1088–1096 | date = December 2011 | pmid = 21733058 | doi = 10.1111/j.1463-1326.2011.01463.x | s2cid = 1092260 | publication-date = October 27, 2011 }}</ref>

<ref name=takedapr28864>{{cite press release |url=https://www.takeda.com/en-us/newsroom/news-releases/2008/takeda-submits-new-drug-application-for-alogliptin-syr-322-in-the-u.s/ |title=Takeda Submits New Drug Application for Alogliptin (SYR-322) in the U.S. |date=January 3, 2008 |access-date=March 11, 2021 |publisher=[[Takeda Pharmaceutical Company]] }}</ref>

}}

== External links ==

* {{Commons category-inline}}

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/850649-61-5 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Alogliptin }}

[[Category:Dipeptidyl peptidase-4 inhibitors]]

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[[Category:Imides]]

[[Category:Pyrimidinediones]]

[[Category:Enantiopure drugs]]

[[Category:Drugs developed by Takeda Pharmaceutical Company]]

[[Category:Sanofi]]