Chemistry:Vildagliptin
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Galvus, Zavamet others |
| Other names | LAF237 |
| AHFS/Drugs.com | UK Drug Information |
| License data | |
| Pregnancy category |
|
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status |
|
| 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 | Kidney |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C17H25N3O2 |
| Molar mass | 303.406 g·mol−1 |
| 3D model (JSmol) | |
| Solubility in water | Freely Soluble in water mg/mL (20 °C) |
| |
| |
  (what is this?) (verify) | |
Vildagliptin, sold under the brand name Galvus and 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.
It was approved by the EMA in 2007.[4]
Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus.[2]
Combination with metformin
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.[5]
Adverse effects
Adverse effects observed in clinical trials include nausea, hypoglycemia, tremor, headache and dizziness. Rare cases of hepatoxicity have been reported.[6]
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.[7][8] 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."[9]
See also
- Development of dipeptidyl peptidase-4 inhibitors
- Dipeptidyl peptidase-4 (CD26)
References
- ↑ 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. http://www.whocc.no/atcddd/new_atc_ddd.html#ATCDDD_FINAL.
- ↑ 2.0 2.1 "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): 2078–2084. May 2004. doi:10.1210/jc.2003-031907. PMID 15126524.
- ↑ 3.0 3.1 "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 214 (3): 829–835. June 1993. doi:10.1111/j.1432-1033.1993.tb17986.x. PMID 8100523.
- ↑ Mathieu, Chantal; Degrande, Evy (December 2008). "Vildagliptin: a new oral treatment for type 2 diabetes mellitus". Vascular Health and Risk Management 4 (6): 1349–1360. ISSN 1176-6344. PMID 19337548. PMC 2663430. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663430/.
- ↑ "EU approves Novartis's Eucreas diabetes drug". Reuters. February 25, 2008. https://www.reuters.com/article/companyNews/idUSZAT00747520080225.
- ↑ "Galvus". www.ema.europa.eu. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf.
- ↑ "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): 1604–1615. July 2009. doi:10.2337/db09-0058. PMID 19403868.
- ↑ "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): 2595–2604. July 2013. doi:10.2337/db12-1686. PMID 23524641.
- ↑ "Pancreatic safety of incretin-based drugs--FDA and EMA assessment". The New England Journal of Medicine 370 (9): 794–797. February 2014. doi:10.1056/NEJMp1314078. PMID 24571751.
External links
- "Vildagliptin". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/vildagliptin.
 |  |
