Vildagliptin
Encyclopedia
Vildagliptin 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.
Novartis has since withdrawn its intent to submit vildagliptin to the FDA, as of July 2008. The Food and Drug Administration
had demanded additional clinical data before it could approve vildagliptin including extra evidence that skin lesions and kidney
impairment seen during an early study
on animals have not occurred in human trials.
While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency
for use within the EU and is listed on the Australian PBS with certain restrictions.
has also approved a new oral treatment released by Novartis, called Eucreas, a combination of vildagliptin and metformin
.
The risk of cancer suppression with DPP-4 down-regulation applies to all the DPP-4 inhibitors on the market in addition to vildagliptin (sitagliptin and saxagliptin)
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1
Glucagon-like peptide-1
Glucagon-like peptide-1 is derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. The biologically active forms of GLP-1 are: GLP-1- and GLP-1-NH2...
and GIP
Glucose-dependent insulinotropic peptide
Gastric inhibitory polypeptide , also known as the glucose-dependent insulinotropic peptide is a member of the secretin family of hormones....
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.
Novartis has since withdrawn its intent to submit vildagliptin to the FDA, as of July 2008. The Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
had demanded additional clinical data before it could approve vildagliptin including extra evidence that skin lesions and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
impairment seen during an early study
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
on animals have not occurred in human trials.
While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
for use within the EU and is listed on the Australian PBS with certain restrictions.
Combination with metformin
The EMEAEuropean Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
has also approved a new oral treatment released by Novartis, called Eucreas, a combination of vildagliptin and metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
.
Cancer risk of DPP-4 inhibitors
The DPP-4 enzyme is known to be involved in the suppression of certain malignancies, particularly in limiting the tissue invasion of these tumours. Inhibiting the DPP-4 enzymes may allow some cancers to progress. A study of DPP-4 inhibition in human non-small cell lung cancer (NSCLC) concluded that "DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells.The risk of cancer suppression with DPP-4 down-regulation applies to all the DPP-4 inhibitors on the market in addition to vildagliptin (sitagliptin and saxagliptin)
Synthetic Chemistry
Source: 1-3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: A Potent, Selective, and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic PropertiesSee also
- dipeptidyl peptidase-4Dipeptidyl peptidase-4Dipeptidyl peptidase-4 , also known as adenosine deaminase complexing protein 2 or CD26 is a protein that, in humans, is encoded by the DPP4 gene.-Function:...
(CD26) - Development of dipeptidyl peptidase-4 inhibitorsDevelopment of dipeptidyl peptidase-4 inhibitorsDipeptidyl peptidase-4 inhibitors are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 and are a potent treatment for type 2 diabetes...
External links
– Vildagliptin – About DPP-4- The race to get DPP-4 inhibitors to market – Forbes.com
- Merck's March Madness – Forbes.com