Vildagliptin

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Vildagliptin
Skeletal formula
Ball-and-stick model
Clinical data
Trade names Galvus/vildagluse/Gliptus
Synonyms (2S)-1-{2-[(3-hydroxy-1-adamantyl)amino]acetyl}pyrrolidine-2-carbonitrile
AHFS/Drugs.com International Drug Names
License data
Pregnancy
category
  • Not recommended
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability 85%
Protein binding 9.3%
Metabolism Mainly hydrolysis to inactive metabolite; CYP450 not appreciably involved
Elimination half-life 2 to 3 hours
Excretion Renal
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.158.712 Edit this at Wikidata
Chemical and physical data
Formula C17H25N3O2
Molar mass 303.399 g/mol
3D model (JSmol)
Solubility in water Freely Soluble in water mg/mL (20 °C)
 ☒N☑Y (what is this?)  (verify)

Vildagliptin (previously LAF237, trade names Galvus, Zomelis,) 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 has been shown to reduce hyperglycemia in type 2 diabetes mellitus.[2]

Combination with metformin[edit]

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 effects[edit]

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]

See also[edit]

References[edit]

  1. ^ WHO International Working Group for Drug Statistics Methodology (August 27, 2008). "ATC/DDD Classification (FINAL): New ATC 5th level codes". WHO Collaborating Centre for Drug Statistics Methodology. Archived from the original on May 6, 2008. Retrieved September 5, 2008.
  2. ^ a b Ahrén, B; Landin-Olsson, M; Jansson, PA; Svensson, M; Holmes, D; Schweizer, A (2004). "Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes". The Journal of Clinical Endocrinology and Metabolism. 89 (5): 2078–84. doi:10.1210/jc.2003-031907. PMID 15126524.
  3. ^ a b Mentlein, R; Gallwitz, B; Schmidt, WE (1993). "Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum". European Journal of Biochemistry / FEBS. 214 (3): 829–35. doi:10.1111/j.1432-1033.1993.tb17986.x. PMID 8100523.
  4. ^ "EU approves Novartis's Eucreas diabetes drug". Reuters. February 25, 2008.
  5. ^ "Galvus" (PDF). www.ema.europa.eu. Retrieved July 29, 2018.
  6. ^ Matveyenko AV, Dry S, Cox HI, et al. (July 2009). "Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin". Diabetes. 58 (7): 1604–15. doi:10.2337/db09-0058. PMC 2699878. PMID 19403868.
  7. ^ Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC (July 2013). "Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors". Diabetes. 62 (7): 2595–604. doi:10.2337/db12-1686. PMC 3712065. PMID 23524641.
  8. ^ Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; De Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis (2014). "Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment — NEJM". New England Journal of Medicine. 370 (9): 794–7. doi:10.1056/NEJMp1314078. PMID 24571751.

External links[edit]