Alogliptin

Last updated
Alogliptin
Alogliptin.svg
Clinical data
Trade names Nesina, Vipidia
Kazano, Vipidomet (with metformin)
Oseni, Incresync (with pioglitazone)
Other namesSYR-322
AHFS/Drugs.com Monograph
MedlinePlus a613026
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU:Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 100%
Protein binding 20%
Metabolism Limited, liver (CYP2D6- and 3A4-mediated)
Elimination half-life 12–21 hours
Excretion Kidney (major) [1] and fecal (minor)
Identifiers
  • 2-({6-[(3R)-3-Aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)benzonitrile
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.256.501 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H21N5O2
Molar mass 339.399 g·mol−1
3D model (JSmol)
  • N#Cc3ccccc3CN\1C(=O)N(C)C(=O)/C=C/1N2CCC[C@@H](N)C2
  • InChI=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 Yes check.svgY
  • Key:ZSBOMTDTBDDKMP-OAHLLOKOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Alogliptin, sold under the brand names Nesina and Vipidia, [2] [3] is an oral anti-diabetic drug in the DPP-4 inhibitor (gliptin) class. [4] 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. [1] Alogliptin and other gliptins are commonly used in combination with metformin in people whose diabetes cannot adequately be controlled with metformin alone. [1]

Contents

In April 2016, the U.S. Food and Drug Administration (FDA) added a warning about increased risk of heart failure. [5] It was developed by Syrrx, a company which was acquired by Takeda Pharmaceutical Company in 2005. [6] In 2020, it was the 295th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [7] [8]

Medical uses

Alogliptin is a dipeptidyl peptidase-4 inhibitor (DDP-4) that decreases blood sugar levels similar to other DPP-4 inhibitors. [9]

Side effects

Adverse events include hypoglycemia, [10] [11] [12] pruritus (itch), [3] nasopharyngitis, headache, and upper respiratory tract infection. [13] It may also cause joint pain that can be severe and disabling. [14] Like other DDP-4 inhibitors, alogliptin is weight-neutral. [1]

A 2014 letter to the editor claimed alogliptin is not associated with increased risk of cardiovascular events. [15] [ better source needed ] In April 2016, the U.S. Food and Drug Administration (FDA) added a warning about increased risk of heart failure. [5]

Market access

Alogliptin tablets sales in mainland China. Specification is 25 mg x 10 tablets. Nesina Sales In China.jpg
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 United States Food and Drug Administration (FDA), [16] after positive results from Phase III clinical trials. [2] In September 2008, the company also filed for approval in Japan, [17] winning approval in April 2010. [16] The company also filed a Marketing Authorization Application elsewhere outside the United States, which was withdrawn in June 2009 needing more data. [17] 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. [16] In 2012, Takeda received a negative response from the FDA on both of these NDAs, citing a need for additional data. [16]

In 2013, the FDA approved the drug in three formulations: as a stand-alone with the brand-name Nesina, [13] combined with metformin using the name Kazano, [18] and when combined with pioglitazone as Oseni. [19]

References

  1. 1 2 3 4 "www.aace.com" (PDF). Archived from the original (PDF) on 2018-11-01.
  2. 1 2 "Takeda Submits New Drug Application for Alogliptin (SYR-322) in the U.S." (Press release). Takeda Pharmaceutical Company. January 3, 2008. Retrieved March 11, 2021.
  3. 1 2 "Vipidia" (PDF). European Medicines Agency. Archived from the original (PDF) on 1 November 2018. Retrieved 31 March 2024.
  4. ↑ Feng J, Zhang Z, Wallace MB, Stafford JA, Kaldor SW, Kassel DB, et al. (May 2007). "Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV". Journal of Medicinal Chemistry. 50 (10): 2297–2300. doi:10.1021/jm070104l. PMID   17441705.
  5. 1 2 "FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin". U.S. Food and Drug Administration (FDA). Retrieved 16 March 2018.
  6. ↑ "The San Diego Union-Tribune - San Diego, California & National News".
  7. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  8. ↑ "Alogliptin - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  9. ↑ Saisho Y (2015). "Alogliptin benzoate for management of type 2 diabetes". Vascular Health and Risk Management. 11: 229–243. doi: 10.2147/VHRM.S68564 . PMC   4401208 . PMID   25914541.
  10. ↑ Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K (September 2011). "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". Current Medical Research and Opinion. 27 (9): 1781–1792. doi:10.1185/03007995.2011.599371. PMID   21806314. S2CID   24082863.
  11. ↑ Kutoh E, Ukai Y (June 2012). "Alogliptin as an initial therapy in patients with newly diagnosed, drug naïve type 2 diabetes: a randomized, control trial". Endocrine. 41 (3) (published January 17, 2012): 435–441. doi:10.1007/s12020-012-9596-0. PMID   22249941. S2CID   45948727.
  12. ↑ Bosi E, Ellis GC, Wilson CA, Fleck PR (December 2011). "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". Diabetes, Obesity & Metabolism. 13 (12) (published October 27, 2011): 1088–1096. doi:10.1111/j.1463-1326.2011.01463.x. PMID   21733058. S2CID   1092260.
  13. 1 2 "Highlights of Prescribing Information: Nesina" (PDF). US Food and Drug Administration. Retrieved 31 March 2024.[ dead link ]
  14. ↑ "DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain". U.S. Food and Drug Administration (FDA). 2015-08-28. Archived from the original on December 9, 2019. Retrieved 1 September 2015.
  15. ↑ White WB, Zannad F (January 2014). "Saxagliptin, alogliptin, and cardiovascular outcomes". The New England Journal of Medicine. 370 (5): 484. doi:10.1056/NEJMc1313880. PMID   24482824.
  16. 1 2 3 4 Grogan K (April 26, 2012), "FDA wants yet more data on Takeda diabetes drug alogliptin", PharmaTimes , PharmaTimes, PharmaTimes online, retrieved April 26, 2012
  17. 1 2 "GEN News Highlights: Takeda Pulls MAA for Type 2 Diabetes Therapy". Genetic Engineering & Biotechnology News. June 4, 2009.
  18. ↑ "Highlights of Prescribing Information: Kazano" (PDF). US Food and Drug Administration. Retrieved 31 March 2024.[ dead link ]
  19. ↑ "Highlights of Prescribing Information: Oseni" (PDF). US Food and Drug Administration. Retrieved 31 March 2024.
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