Inhibitors of Dipeptidyl peptidase 4 , also DPP-4 inhibitors, are a class of oral hypoglycemics that block DPP-4. They can be used to treat diabetes mellitus type 2.
The first agent of the class - sitagliptin - was approved by the FDA in 2006.[1] Sitagliptin entered the Australian drug market in late 2007 for the treatment of difficult-to-control diabetes mellitus type 2.
Their mechanism of action is thought to result from increased Incretin levels (GLP-1 and GIP),[2][3][4] which inhibit glucagon release, the effect of which, in turn, decreases blood glucose, but, more significant, increases insulin secretion and decreases gastric emptying.
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Examples
Drugs belonging to this class are :
- sitagliptin[5] (FDA approved 2006, marketed by Merck_&_Co. under the trade name Januvia),
- vildagliptin[6] (marketed in the EU by Novartis under the trade name Galvus),
- saxagliptin (being developed by Bristol-Myers Squibb, AstraZeneca and Otsuka Pharmaceutical Co.),
- linagliptin (being developed by Boehringer Ingelheim),
- alogliptin (developed by Takeda Pharmaceutical Company, whose FDA application for the product is currently suspended as of June 2009).
Berberine, the common herbal dietery supplement, too inhibits dipeptidyl peptidase-4, which at least partly explains its anti-hyperglycemic activities.[7]
Possible cancer risk
Although extensive long-term, pre-clinical studies of the major DPP-4 inhibitors has failed to show any evidence of potential to cause tumors in laboratory animals, there was one in-vitro (i.e., test tube) study that has raised some questions.[8]
In theory, DPP-4 inhibitors may allow some cancers to progress, since DPP-4 appears to work as a suppressor in the development of cancer and tumours.[9][8][10]
See also
References
- ^ U.S. Food and Drug Administration (October 17, 2006). "FDA Approves New Treatment for Diabetes". Press release. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01492.html. Retrieved 2006-10-17.
- ^ McIntosh CH, Demuth HU, Pospisilik JA, Pederson R (June 2005). "Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents?". Regul. Pept. 128 (2): 159–65. doi:. PMID 15780435.
- ^ Behme MT, Dupré J, McDonald TJ (April 2003). "Glucagon-like peptide 1 improved glycemic control in type 1 diabetes". BMC Endocr Disord 3 (1): 3. doi:. PMID 12697069.
- ^ Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ (June 1995). "Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM". Diabetes 44 (6): 626–30. PMID 7789625.
- ^ Banting and Best Diabetes Centre at UT sitagliptin
- ^ Banting and Best Diabetes Centre at UT vildagliptin
- ^ Al-Masri IM, Mohammad MK, Tahaa MO.(July 2009)"Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine". J Enzyme Inhib Med Chem.PubMed
- ^ a b Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (December 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regul. Pept. 137 (3): 147–55. doi:. PMID 16908079.
- ^ Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histol. Histopathol. 19 (4): 1345–51. PMID 15375776. http://www.hh.um.es/Abstracts/Vol_19/19_4/19_4_1345.htm.
- ^ Wesley UV, McGroarty M, Homoyouni A (February 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Res. 65 (4): 1325–34. doi:. PMID 15735018.
Further reading
- Herper, Matthew; Langreth, Robert (27 April 2006), "Diabetes Drugs to Watch", Forbes.com, Pharmaceuticals, http://www.forbes.com/2005/08/02/pharmaceuticals-biotechnology-diabetes-cx_mh_rl_diabetestearsheet.html, retrieved 26 April 2009
See pages of this article for Galvus aka LAF237 (Novartis) and Januvia aka MK-0431 (Merck) - Nielson, Loretta L. (15 May 2005), "Incretin mimetics and DPP-IV inihibitors for the treatment of type 2 diabetes", Drug Discovery Today, Reviews (Elsevier) 10 (10/24): 703–710
Includes table describing an overview of type 2 diabetes drug therapies; 76 references.
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