Vildagliptin

 Vildagliptin, sold under the brand name Galvus among others, is an oral anti-hyperglycemic agent (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1[2][3] and GIP[3] 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
Skeletal formula
Ball-and-stick model
Clinical data
Trade namesGalvus, Xiliarx, Jalra, others
Other namesLAF237
AHFS/Drugs.comUK Drug Information
License data
  • EU EMA: by INN
Pregnancy
category
  • Not recommended
Routes of
administration		By mouth
ATC code
  • A10BH02 (WHO)
    A10BD08 (WHO) (with metformin)[1]
Legal status
Legal status
  • UK: POM (Prescription only)
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability85%
Protein binding9.3%
MetabolismMainly hydrolysis to inactive metabolite; CYP450 not appreciably involved
Elimination half-life2 to 3 hours
ExcretionKidney
Identifiers
IUPAC name
  • (S)-1-[N-(3-Hydroxy-1-adamantyl)glycyl]pyrrolidine-2-carbonitrile
CAS Number
  • 274901-16-5 ☒
PubChem CID
  • 6918537
IUPHAR/BPS
  • 6310
DrugBank
  • DB04876 check
ChemSpider
  • 5293734 check
UNII
  • I6B4B2U96P
KEGG
  • D07080 check
ChEMBL
  • ChEMBL142703 check
CompTox Dashboard (EPA)
  • DTXSID80881091 Edit this at Wikidata
ECHA InfoCard100.158.712 Edit this at Wikidata
Chemical and physical data
FormulaC17H25N3O2
Molar mass303.406 g·mol−1
3D model (JSmol)
  • Interactive image
Solubility in waterFreely Soluble in water mg/mL (20 °C)
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 check
  • Key:SYOKIDBDQMKNDQ-XWTIBIIYSA-N check
 ☒check (what is this?)  (verify)

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

Combination with metforminEdit

The European Medicines Agency has also approved a combination of vildagliptin and metformin, vildagliptin/metformin (Eucreas by Novartis) as an oral treatment for type-2 diabetes.[4]

Adverse effectsEdit

Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.[5]

There have been case reports of pancreatitis associated with DPP-4 inhibitors. A group at UCLA reported increased pre-cancerous pancreatic changes in rats and in human organ donors who had been treated with DPP-4 inhibitors.[6][7] 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-4 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."[8]

This article uses material from the Wikipedia article
 Metasyntactic variable, which is released under the 
Creative Commons
Attribution-ShareAlike 3.0 Unported License.