Alogliptin

{{Short description|Anti-diabetic drug}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 454952697

| image = Alogliptin.svg

| alt =

| pronounce =

| tradename = Nesina, Vipidia
Kazano, Vipidomet (with metformin)
Oseni, Incresync (with pioglitazone)

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

| MedlinePlus = a613026

| licence_EU = yes

| DailyMedID = Alogliptin

| licence_US =

| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_US = B

| pregnancy_US_comment =

| pregnancy_category =

| routes_of_administration = By mouth

| ATC_prefix = A10

| ATC_suffix = BH04

| legal_AU = S4

| legal_CA =

| legal_UK =

| legal_US = Rx-only

| legal_EU = Rx-only

| legal_status = Rx-only

| bioavailability = 100%

| protein_bound = 20%

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

| elimination_half-life = 12–21 hours

| excretion = Kidney (major) and fecal (minor)

| IUPHAR_ligand = 6319

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

| CAS_number = 850649-61-5

| PubChem = 11450633

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

| DrugBank =

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

| ChEBI = 72323

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

| UNII = JHC049LO86

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D06553

| 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

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

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

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

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

| ChemSpiderID = 9625485

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

| 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

}}

Alogliptin, sold under the brand names Nesina and Vipidia,{{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 }} is an oral anti-diabetic drug in the DPP-4 inhibitor (gliptin) class. 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. Alogliptin and other gliptins are commonly used in combination with metformin in people whose diabetes cannot adequately be controlled with metformin alone.{{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 }}

In April 2016, the U.S. Food and Drug Administration (FDA) added a warning about increased risk of heart failure.{{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 }} It was developed by Syrrx, a company which was acquired by Takeda Pharmaceutical Company in 2005.{{Cite web|url=http://www.utsandiego.com/uniontrib/20050208/news_1b8syrrx.html|title = The San Diego Union-Tribune - San Diego, California & National News}} In 2020, it was the 295th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022}}{{cite web | title = Alogliptin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Alogliptin | access-date = 7 October 2022}}

Medical uses

Alogliptin is a dipeptidyl peptidase-4 inhibitor (DDP-4) that decreases blood sugar levels similar to other DPP-4 inhibitors.{{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 }}

Side effects

Adverse events include hypoglycemia, pruritis (itching), nasopharyngitis, headache, and upper respiratory tract infection. It may also cause joint pain that can be severe and disabling.{{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}} Like other DDP-4 inhibitors, alogliptin is weight-neutral.

A 2014 letter to the editor claimed alogliptin is not associated with increased risk of cardiovascular events.{{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 }}{{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.

Market access

File:Nesina Sales In China.jpg

In December 2007, Takeda submitted a New Drug Application (NDA) for alogliptin to the United States Food and Drug Administration (FDA), after positive results from Phase III clinical trials. In September 2008, the company also filed for approval in Japan, winning approval in April 2010. The company also filed a Marketing Authorization Application elsewhere outside the United States, which was withdrawn in June 2009 needing more data. 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. In 2012, Takeda received a negative response from the FDA on both of these NDAs, citing a need for additional data.

In 2013, the FDA approved the drug in three formulations: as a stand-alone with the brand-name 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}} combined with metformin using the name 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}} and when combined with pioglitazone as 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}}{{clear}}

References

{{reflist|refs=

{{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}}

{{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 }}

{{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 }}

{{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 }}

{{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 }}

{{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 }}

{{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 }}

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