Better Known as: Januvia
- Marketed By: Merck & Co.
- Major Indication: Hyperglycemia & Type II Diabetes
- Drug Class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor
- Date of FDA Approval (Patent Expiration): 2006 (2017)
- 2009 Sales: $2.4 Billion
- Importance: One of the best selling treatments for Type II Diabetes. Often used in combination with Metformin, the first line anti-diabetic medication (Combination sold as Janumet). Has an excellent side-effect profile with a relatively low incidence of hypoglycemia an weight gain. Increasing evidence that all DPP-4 inhibitors can to certain malignant cancers.[1]
- See Pharmaceutical Drugs for more information about other drugs and diseases.
Mechanism of Action
Type II Diabetes is a chronic metabolic disorder caused by pancrease β-cell dysfunction, deficiency in insulin secretion or insulin resistance, and/or increased hepatic glucose production. Numerous complex systems are involved in this disorder, with several protein serving as therapeutic targets. Dipeptidyl Peptidase-4 (DPP-4) is an antigenic membrane serine exopeptidase that cleaves proline dipeptides form the N-terminal end of protein substrates. DPP-4 plays a major role in glucose metabolism as it is responsible for the degradation of incretins, most notably Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIp). Incretins are a group of gastrointestinal hormones that stimulate insulin biosynthesis and inhibit glucagon secretion after consuming high glucose meals. Sitagliptin is a competitive inhibitor of DPP-4. By inhibiting DPP-4 and subsequently preventing the enzymatic degradation of GLP-1 and GIP, these incretins are able to potentiate the secretion of insulin and suppress the release of glucagon by the pancreas. The result is controlled blood-glucose levels, a major concern for diabetics.
Pharmacokinetics
For Pharmacokinetic Data References, see: References
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References
- ↑ Wesley UV, McGroarty M, Homoyouni A. Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res. 2005 Feb 15;65(4):1325-34. PMID:15735018 doi:10.1158/0008-5472.CAN-04-1852
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