Linagliptin

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Linagliptin
Linagliptin.svg
Clinical data
Pronunciation /ˌlɪnəˈɡlɪptɪn/ LIN-ə-GLIP-tin
Trade names Tradjenta, Trajenta, Trazenta
Other namesBI-1356
AHFS/Drugs.com Monograph
MedlinePlus a611036
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~30% (Tmax = 1.5 hours)
Protein binding 75–99% (concentration-dependent)
Metabolism Minimal (~10% metabolized)
Metabolites Pharmacologically inactive
Elimination half-life ~24 hours
Excretion Feces (80%), urine (5%) [6]
Identifiers
  • 8-[(3R)-3-Aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C25H28N8O2
Molar mass 472.553 g·mol−1
3D model (JSmol)
Melting point 202 °C (396 °F)
  • CC#CCN1C2=C(N=C1N3CCC[C@H](C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C
  • InChI=1S/C25H28N8O2/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3/t17-/m1/s1 X mark.svgN
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Linagliptin, sold under the brand name Tradjenta among others, is a medication used to treat type 2 diabetes (but not type 1) in conjunction with exercise and diet. [8] [9] It is generally less preferred than metformin and sulfonylureas as an initial treatment. [8] [10] It is taken by mouth. [8]

Contents

Common side effects include inflammation of the nose and throat. [8] Serious side effects may include angioedema, pancreatitis, joint pain. [10] [8] Use in pregnancy and breastfeeding is not recommended. [10] Linagliptin is a dipeptidyl peptidase-4 inhibitor [8] that works by increasing the production of insulin and decreasing the production of glucagon by the pancreas. [8]

Linagliptin was approved for medical use in the United States, [11] Japan, the European Union, Canada, and Australia in 2011. [8] [12] In 2020, it was the 293rd most commonly prescribed medication in the United States, with more than 1 million prescriptions. [13] [14] From August 2021 linagliptin became available as a generic medicine in the US. [15]

Medical uses

Linagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. [6]

Side effects

Common side effects of linagliptin may include:
Upper respiratory tract infection, Headache, Hypoglycemia, Joint pain, Allergic reactions. [6] [16]

Mechanism of action

Linagliptin belongs to a class of drugs called DPP-4 inhibitors. [6] It is a reversible, competitive inhibitor of DPP-4. GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP) are broken down more slowly when this enzyme is inhibited. While glucagon release from pancreatic beta cells is inhibited, GLP-1 and GIP promote the production of insulin from the organ's beta cells. Together, these effects improve insulin release in response to glucose and decrease the liver's breakdown of glycogen [17]

Names

Linagliptin is the international nonproprietary name (INN). [18] Trade names: Trajenta, [19] Tradjenta.

See also

Related Research Articles

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

<span class="mw-page-title-main">Incretin</span> Group of gastrointestinal hormones

Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.

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

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<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">Glucagon-like peptide-1</span> Gastrointestinal peptide hormone Involved in glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

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

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<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

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<span class="mw-page-title-main">Daniel J. Drucker</span> Canadian endocrinologist (born 1956)

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<span class="mw-page-title-main">Semaglutide</span> Anti-diabetic and anti-obesity medication

Semaglutide is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management. It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain. It can be administered by subcutaneous injection or taken orally. It is sold under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight loss.

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References

  1. ↑ "Linagliptin, tablet, 5 mg, Trajenta". Pharmaceutical Benefits Scheme (PBS). July 2012. Archived from the original on 31 March 2015. Retrieved 26 September 2014.
  2. ↑ "AusPAR: Linagliptin". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
  3. ↑ "Trajenta Product information". Health Canada. 25 April 2012. Archived from the original on 27 September 2021. Retrieved 3 October 2022.
  4. ↑ "Trajenta 5 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 27 September 2021. Archived from the original on 19 January 2022. Retrieved 3 October 2022.
  5. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  6. 1 2 3 4 5 "Tradjenta- linagliptin tablet, film coated". DailyMed. 21 April 2022. Archived from the original on 15 August 2022. Retrieved 3 October 2022.
  7. ↑ "Trajenta EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 29 December 2019. Retrieved 11 February 2020.
  8. 1 2 3 4 5 6 7 8 "Linagliptin Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 6 April 2019. Retrieved 6 April 2019.
  9. ↑ Neumiller JJ (March 2012). "Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus". The Annals of Pharmacotherapy. 46 (3): 358–67. doi:10.1345/aph.1Q522. PMID   22318932. S2CID   207264493.
  10. 1 2 3 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 680. ISBN   9780857113382.
  11. ↑ "Drug Approval Package: Tradjenta (linagliptin) Tablets NDA #201280". U.S. Food and Drug Administration (FDA). 7 June 2011. Archived from the original on 3 April 2022. Retrieved 3 October 2022.
  12. ↑ "10 years". Boehringer Ingelheim Limited. Archived from the original on 3 October 2022. Retrieved 3 October 2022.
  13. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  14. ↑ "Linagliptin - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  15. ↑ "Linagliptin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 25 September 2021. Retrieved 24 September 2021.
  16. ↑ "DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain". U.S. Food and Drug Administration (FDA). 28 August 2015. Archived from the original on 13 December 2019. Retrieved 1 September 2015.
  17. ↑ "Linagliptin". go.drugbank.com. Retrieved 31 December 2023.
  18. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary names: List 61" (PDF). World Health Organization. p. 66. Archived (PDF) from the original on 3 October 2020. Retrieved 10 November 2016.
  19. ↑ "Linagliptin: medicine to treat type 2 diabetes". NHS UK. 25 March 2022. Retrieved 21 November 2022.
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