Vildagliptin

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.

Vildagliptin

Clinical data
Trade names	Galvus, Zavamet others
Other names	LAF237
AHFS/Drugs.com	UK 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
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
IUPAC name (S)-1-[N-(3-Hydroxy-1-adamantyl)glycyl]pyrrolidine-2-carbonitrile
CAS Number	274901-16-5 N
PubChem CID	6918537
IUPHAR/BPS	6310
DrugBank	DB04876 Y
ChemSpider	5293734 Y
UNII	I6B4B2U96P
KEGG	D07080 Y
ChEMBL	ChEMBL142703 Y
CompTox Dashboard (EPA)	DTXSID80881091
ECHA InfoCard	100.158.712
Chemical and physical data
Formula	C17H25N3O2
Molar mass	303.406 g·mol−1
3D model (JSmol)	Interactive image
Solubility in water	Freely 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 Y Key:SYOKIDBDQMKNDQ-XWTIBIIYSA-N Y
NY (what is this?)  (verify)

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

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. Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A (May 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): 2078–2084. doi:10.1210/jc.2003-031907. PMID 15126524.
3. Mentlein R, Gallwitz B, Schmidt WE (June 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. 214 (3): 829–835. doi:10.1111/j.1432-1033.1993.tb17986.x. PMID 8100523.
4. Mathieu C, Degrande E (December 2008). "Vildagliptin: a new oral treatment for type 2 diabetes mellitus". Vascular Health and Risk Management. 4 (6): 1349–1360. doi:10.2147/vhrm.s3005. PMC 2663430. PMID 19337548.
5. "EU approves Novartis's Eucreas diabetes drug". Reuters. February 25, 2008.
6. "Galvus" (PDF). www.ema.europa.eu. Retrieved July 29, 2018.
7. Matveyenko AV, Dry S, Cox HI, Moshtaghian A, Gurlo T, Galasso R, 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): 1604–1615. doi:10.2337/db09-0058. PMC 2699878. PMID 19403868.
8. 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): 2595–2604. doi:10.2337/db12-1686. PMC 3712065. PMID 23524641.
9. Egan AG, Blind E, Dunder K, de Graeff PA, Hummer BT, Bourcier T, et al. (February 2014). "Pancreatic safety of incretin-based drugs--FDA and EMA assessment". The New England Journal of Medicine. 370 (9): 794–797. doi:10.1056/NEJMp1314078. PMID 24571751.

External links

• "Vildagliptin". Drug Information Portal. U.S. National Library of Medicine.