C-peptide, and insulin secretion rates over glycemic excursions was significantly enhanced un- der vildagliptin treatment. Surprisingly, however, the nu- merical incretin effect (based on insulin, C-peptide con- centrations, and insulin secretion rates measured after oral and iv glucose testing) did not differ between vildagliptin and placebo. To further elucidate these findings, the au- thors show that the insulin secretory response to glucose is enhanced with vildagliptin treatment not only by oral load but also after iv load, contributing to the numerical similarity of the calculated incretin effects. This raises sev- eral questions regarding calculation of the incretin effect and its purported physiological basis. Oral glucose load was shown to produce a greater insulin response than iv injection of glucose in the 1960s (7, 8), and the incretin effect was defined as the difference in B-cell secretory re- sponse to oral or iv glucose stimuli (9-11). The calculation was based on the assumption that after oral glucose ad- ministration, B-cells are stimulated by the elevated plasma glucose as well as by the additional stimulation of incretin hormones not activated during iv glucose loading. Vardarli et al. (6) have now demonstrated that there is a minor rise in the intact GLP-1 concentration during iv glucose ad- ministration after vildagliptin exposure. Furthermore, this rise may underlie the enhanced insulin secretory response after iv glucose load that results in the substantial insulin response used in calculating the incretin effect. Vildaglip- tin was found not to change the numerical incretin effect compared with placebo.
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