Saxagliptin: A New Drug for the Treatment of Type 2 Diabetes

E-ISSN： 1875-5607|10|8|759-765

ISSN： 1389-5575

Source： Mini Reviews in Medicinal Chemistry, Vol.10, Iss.8, 2010-07, pp. : 759-765

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Abstract

Saxagliptin (BMS-477118), a recently FDA approved drug for the management of T2DM, has been developed by Bristol-Myers Squibb and AstraZeneca under the trade name Onglyza™. Saxagliptin is a nitrile-containing selective, potent, reversible and durable DPP IV inhibitor developed as an alternative second-line to Metformin in place of a sulphonylurea. Saxagliptin increases and prolongs the action of incretin hormones by inhibiting the DPP IV enzyme that inactivates incretins usually within minutes. Saxagliptin is well absorbed and has low plasma protein binding and displays slow-binding properties to DPP IV. Saxagliptin is metabolized in vivo to form an active metabolite (BMS-510849), which is twofold less potent than the parent molecule. The X-ray crystallography revealed that Saxagliptin is covalently bound to the DPP IV active site. In drug-naive patients with T2DM and inadequate glycemic control, once-daily Saxagliptin monotherapy for 24 wks demonstrated clinically meaningful with no weight gain and was generally well tolerated.