indication

Investigated for use/treatment in diabetes mellitus type 2.Z

mechanism of action

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of Type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

absorption

Following the 5 mg once daily dose, the median time to maximum concentration is 2 hours.

half life

2.5 hours

route of elimination

Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.

drug interactions

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Limit saxagliptin dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant administration of a strong CYP3A4 inhibitor (e.g., ketoconazole). Monitor for decreased saxagliptin levels/effects with discontinuation of concomitant CYP3A4 inhibitor.

Somatropin recombinant: Somatropin may antagonize the hypoglycemic effect of saxagliptin. Monitor for changes in fasting and postprandial blood sugars.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of saxagliptin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of saxagliptin if voriconazole is initiated, discontinued or dose changed.