( 12 CLINICAL PHARMACOLOGY 12.1 ...)Late Breaking Data Released at ADA Showed that the Investigational,Use of Januvia and Metformin as Initial Combination Therapy,Provided Significant Glucose Lowering Efficacy over 54 Weeks in,Patients with Type 2 Diabetes,Health

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by JANUVIA, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, JANUVIA increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses. 12.2 Pharmacodynamics General In patients with type 2 diabetes, administration of JANUVIA led to inhibition of DPP-4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased responsiveness of insulin release to glucose, resulting in higher C-peptide and insulin concentrations. The rise in insulin with the decrease in glucagon was associated with lower fasting glucose concentrations and reduced gluc
'"/>




Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
Related medicine technology :

1. VeroScience Late-Breaking Abstract on Cycloset (A Quick Release Formulation of Bromocriptine Mesylate) Accepted for Poster Presentation at American Diabetes Association 67th Scientific Sessions
2. Pilot Phase 3 Results of NovaCardias KW-3902 for Acute Congestive Heart Failure Presented at Late-Breaking Session of Heart Failure Congress 2007
3. Breaking Multi-Center Study: Masimo SET Pulse Oximetry Technology Shown to Significantly Lower Instances of Severe Retinopathy of Prematurity in Extremely Low Birth Weight Infants
4. Bentley Late Breaking Abstract Accepted for Poster Presentation at American Diabetes Association Scientific Sessions
5. Cougar Biotechnology Presents Positive CB7630 Clinical Data at AACR Annual Meeting Late-Breaking Clinical Trials Session
6. Everest Data on Short- and Long-Term Use of Otsukas Investigational Novel Treatment, Tolvaptan, Published in Journal of the American Medical Association and Featured in ACCs Late Breaking Clinical Trials
7. Lupus Foundation of America Statement on Results for Clinical Study of CellCept Released by Aspreva Pharmaceutical Company
8. An Investigational Study Released at ADA Showed that Initial Combination Therapy with Januvia (sitagliptin) and Metformin Led to Improvement in Markers of Beta Cell Function in Patients with Type 2 Diabetes
9. Amlodipine and Olmesartan Study Results Released;Late Breaker Presented at American Society of Hypertension Twenty-Second Annual Scientific Meeting (ASH 2007)
10. Amlodipine and Olmesartan Study Results Released; Late Breaker Presented at American Society of Hypertension Twenty-Second Annual Scientific Meeting (ASH 2007)
11. New Anti-Rejection Medication 6-Month Results for Heart Transplant Recipients to Be Released at International Heart and Lung Transplant Meeting