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Glu 16 , Val 19 and Arg 20 were determined to be the essential determinants of Ex4(9-39)'s antagonism, in agreement with earlier chimaeric studies that demonstrated that the E 16 EAVRL sequence within the N-terminally truncated Ex4 was the determinant of its greater affinity over that of GLP-1(15-36)amide
3,4 These incretins are rapidly inactivated by DPP-4, an enzyme expressed throughout the vascular endothelial cells, venous capillary beds, gut, liver, lungs, and kidneys
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In its Complete Response Letter, the FDA did not identify efficacy or safety problems with the application, according to the companies

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