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] pruritis (itching), [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]

Related Research Articles

<span class="mw-page-title-main">Metformin</span> Medication used to treat diabetes by reducing glucose levels

Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is not associated with weight gain and is taken by mouth.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Rosiglitazone</span> Chemical compound

Rosiglitazone is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug or for use in combination with metformin or with glimepiride. First released in 1999, annual sales peaked at approximately $2.5-billion in 2006; however, following a meta-analysis in 2007 that linked the drug's use to an increased risk of heart attack, sales plummeted to just $9.5-million in 2012. The drug's patent expired in 2012.

<span class="mw-page-title-main">Pioglitazone</span> Chemical compound

Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Exenatide</span> Medication

Exenatide, sold under the brand name Byetta among others, is a medication used to treat type 2 diabetes. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin.

<span class="mw-page-title-main">Vildagliptin</span> Chemical compound

Vildagliptin, sold under the brand name Galvus and others, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas.

<span class="mw-page-title-main">Dipeptidyl peptidase-4 inhibitor</span> Enzyme blocker and diabetes treatment drug

Inhibitors of dipeptidyl peptidase 4 are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.

<span class="mw-page-title-main">Sitagliptin</span> Diabetes medication

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.

<span class="mw-page-title-main">Saxagliptin</span> Chemical compound

Saxagliptin, sold under the brand name Onglyza, is an oral hypoglycemic of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug.

<span class="mw-page-title-main">Dapagliflozin</span> Diabetes medication

Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type 2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease. It reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

<span class="mw-page-title-main">Linagliptin</span> Chemical compound

Linagliptin, sold under the brand name Tradjenta among others, is a medication used to treat type 2 diabetes in conjunction with exercise and diet. It is generally less preferred than metformin and sulfonylureas as an initial treatment. It is taken by mouth.

Dipeptidyl peptidase-4 inhibitors are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4). They are used in the treatment of type 2 diabetes mellitus. Inhibition of the DPP-4 enzyme prolongs and enhances the activity of incretins that play an important role in insulin secretion and blood glucose control regulation. Type 2 diabetes mellitus is a chronic metabolic disease that results from inability of the β-cells in the pancreas to secrete sufficient amounts of insulin to meet the body's needs. Insulin resistance and increased hepatic glucose production can also play a role by increasing the body's demand for insulin. Current treatments, other than insulin supplementation, are sometimes not sufficient to achieve control and may cause undesirable side effects, such as weight gain and hypoglycemia. In recent years, new drugs have been developed, based on continuing research into the mechanism of insulin production and regulation of the metabolism of sugar in the body. The enzyme DPP-4 has been found to play a significant role.

<span class="mw-page-title-main">Canagliflozin</span> Chemical compound

Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Gemigliptin</span> Chemical compound

Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.

SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

<span class="mw-page-title-main">Trelagliptin</span> Chemical compound

Trelagliptin is a pharmaceutical drug used for the treatment of type 2 diabetes.

<span class="mw-page-title-main">Evogliptin</span> Chemical compound

Evogliptin is an antidiabetic drug in the dipeptidyl peptidase-4 (DPP-4) inhibitor or "gliptin" class of drugs. It was developed by the South Korean pharmaceutical company Dong-A ST and is approved for use in South Korea and Russia. In a meta-analysis involving data from 6 randomized controlled trials, Dutta et. al. demonstrated the good glycaemic efficacy and safety of this medicine as compared to other DPP4 inhibitors like sitagliptin and linagliptin.

<span class="mw-page-title-main">Gosogliptin</span> Chemical compound

Gosogliptin is a drug for the treatment of type II diabetes. It is in the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. It was discovered and developed through Phase 1 and Phase 2 by Pfizer. The crystal structure of DPP-4 in complex with gosogliptin is available. Its metabolism, excretion and pharmacokinetics in rat, dog and human have been described. A cost efficient route has been published. Other studies including Phase 3 studies were conducted in Russia. It is approved for use in Russia.

Canagliflozin/metformin, sold under the brand name Vokanamet among others, is a fixed-dose combination anti-diabetic medication used for the treatment of type 2 diabetes. It is used in combination with diet and exercise. It is taken by mouth.

Pioglitazone/glimepiride, sold under the brand name Duetact among others, is a fixed-dose combination anti-diabetic medication for the treatment of type 2 diabetes. It contains the thiazolidinedione pioglitazone and the sulfonylurea glimepiride. It is taken by mouth.

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.
  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. 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.
  19. ↑ "Highlights of Prescribing Information: Oseni" (PDF). US Food and Drug Administration. Retrieved 31 March 2024.
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