Vildagliptin

Vildagliptin

Systematic (IUPAC) name
(S)-1-[N-(3-hydroxy-1-adamantyl)glycyl]pyrrolidine-2-carbonitrile
Clinical data
Trade names	Galvus
AHFS/Drugs.com	International Drug Names
Licence data	EMA:Link
Pregnancy category	Not recommended
Legal status	UK: POM (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	85%
Protein binding	9.3%
Metabolism	Mainly hydrolysis to inactive metabolite; CYP450 not appreciably involved
Biological half-life	2 to 3 hours
Excretion	Renal
Identifiers
CAS Number	274901-16-5 N
ATC code	A10BH02 (WHO) A10BD08 (with metformin)
PubChem	CID: 6918537
IUPHAR/BPS	6310
DrugBank	DB04876 Y
ChemSpider	5293734 Y
UNII	I6B4B2U96P Y
KEGG	D07080 Y
ChEMBL	CHEMBL142703 Y
Synonyms	(2S)-1-{2-[(3-hydroxy-1-adamantyl)amino]acetyl}pyrrolidine-2-carbonitrile
Chemical data
Formula	C17H25N3O2
Molecular mass	303.399 g/mol
SMILES N#C[C@H]4N(C(=O)CNC13CC2CC(C1)CC(O)(C2)C3)CCC4
InChI InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1 Y Key:SYOKIDBDQMKNDQ-XWTIBIIYSA-N Y
NY (what is this?)  (verify)

Vildagliptin (previously LAF237, trade names Galvus, Zomelis,) is an oral anti-hyperglycemic agent (anti-diabetic drug) of the new 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.

Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus.

Vildagliptin is a unique molecule with dual nature as it manages the glucagon levels in hypoglycemia as well as hyperglycemia.

Combination with metformin

The EMEA has also approved a new oral treatment released by Novartis, called Eucreas, a combination of vildagliptin and metformin.

Adverse Effects

Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.

There have been case reports of pancreatitis associated with DPP-IV inhibitors. A group at UCLA reported increased pre-cancerous pancreatic changes in rats and in human organ donors who had been treated with DPP-IV inhibitors. In response to these reports, the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-IV inhibitors with pancreatic cancer. In a joint letter to the New England Journal of Medicines, the agencies stated that "Both agencies agree that assertions concerning a causal association between incretin-based drugs and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and in the media, are inconsistent with the current data. The FDA and the EMA have not reached a final conclusion at this time regarding such a causal relationship. Although the totality of the data that have been reviewed provides reassurance, pancreatitis will continue to be considered a risk associated with these drugs until more data are available; both agencies continue to investigate this safety signal."

See also

• Development of dipeptidyl peptidase-4 inhibitors
• Dipeptidyl peptidase-4 (CD26)

External links

• Banting and Best Diabetes Centre at UT vildagliptin – Vildagliptin
• Banting and Best Diabetes Centre at UT dpp4 – About DPP-4
• The race to get DPP-4 inhibitors to market – Forbes.com
• Merck's March Madness – Forbes.com