Linagliptin

Linagliptin
Systematic (IUPAC) name

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
Clinical data
Trade names	Tradjenta, Trajenta
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a611036
License data	EU EMA: Trajenta US FDA: Linagliptin
Pregnancy category	US: B (No risk in non-human studies)
Routes of administration	Oral
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	30% oral
Protein binding	75% to 99% in plasma
Identifiers
CAS Number	668270-12-0^Y
ATC code	A10BH05 (WHO)
PubChem	CID 10096344
IUPHAR/BPS	6318
ChemSpider	8271879^N
UNII	3X29ZEJ4R2^Y
KEGG	D09566^Y
ChEMBL	CHEMBL237500^N
Chemical data
Formula	C₂₅H₂₈N₈O₂
Molar mass	472.54 g/mol
SMILES CC#CCN1C2=C(N=C1N3CCC[C@H](C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C
InChI 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^N Key:LTXREWYXXSTFRX-QGZVFWFLSA-N^N
^NY (what is this?) (verify)

Linagliptin (BI-1356, trade names Tradjenta (US), Trajenta (worldwide)) is a DPP-4 inhibitor developed by Boehringer Ingelheim for treatment of type II diabetes.

Linagliptin (once-daily) was approved by the U.S. Food and Drug Administration (FDA) on 2 May 2011 for treatment of type II diabetes.^[1] It is being marketed by Boehringer Ingelheim and Lilly.

Medical uses

Results in 2010 from a Phase III clinical trial of linagliptin showed that the drug can effectively reduce blood sugar.^[2]

Side effects

They may cause severe joint pain.^[3]

Mechanism of action

Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output. Thus, linagliptin stimulates the release of insulin in a glucose-dependent manner and decreases the levels of glucagon in the circulation.

References

H. Spreitzer (September 1, 2008). "Neue Wirkstoffe - BI-1356". Österreichische Apothekerzeitung (in German) (18/2008): 918.
Wang, Y, Serradell, N, Rosa, E, Castaner, R (2008). "BI-1356". Drugs of the Future 33 (6): 473–477. doi:10.1358/dof.2008.033.06.1215244.

↑ "FDA Approves Type 2 Diabetes Drug from Boehringer Ingelheim and Lilly". 3 May 2011.
↑ "Four Phase III Trials Confirm Benefits of BI’s Oral, Once-Daily Type 2 Diabetes Therapy". Genetic Engineering & Biotechnology News. 28 June 2010.
↑ "DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain". FDA. 2015-08-28. Retrieved 1 September 2015.

Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)

Insulin

Sensitizers

Biguanides	Metformin^# Buformin<sp>‡ Phenformin^‡

TZDs/"glitazones" (PPAR)	Ciglitazone^§ Darglitazone^§ Englitazone^§ Lobeglitazone Netoglitazone^§ Pioglitazone Rivoglitazone^† Rosiglitazone Troglitazone^‡

Dual PPAR agonists	Aleglitazar^† Muraglitazar^§ Saroglitazar Tesaglitazar^§

Secretagogues

K+ ATP

Sulfonylureas	1st generation: Acetohexamide Carbutamide Chlorpropamide Metahexamide Tolbutamide Tolazamide 2nd generation: Glibenclamide (Glyburide)^# Glibornuride Glicetanile Gliclazide Gliflumide Glipizide Gliquidone Glisoxepide Glyclopyramide Glimepiride

Meglitinides/"glinides"	Nateglinide Repaglinide Mitiglinide

GLP-1 agonists

DPP-4 inhibitors

GPR40 Free fatty acid receptor 1

Fasiglifam^†

Analogs/other insulins

fast-acting (Insulin lispro
Insulin aspart
Insulin glulisine)
short-acting (Regular insulin)
long-acting (Insulin glargine
Insulin detemir
NPH insulin)
ultra-long-acting (Insulin degludec^†)
inhalable Exubera^‡
Afrezza

Other

Aldose reductase inhibitors	Epalrestat Fidarestat^§ Ranirestat^† Tolrestat^‡ Zenarestat^§

Alpha-glucosidase inhibitors	Acarbose Miglitol Voglibose

Amylin analog	Pramlintide

Sodium glucose transporter (SGLT2) inhibitors	Canagliflozin Dapagliflozin Empagliflozin Remogliflozin^§ Sergliflozin^§ Tofogliflozin^†

Other	Benfluorex^‡ Bromocriptine

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

External links

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