Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 92, Issue 11, Pages 4165-4171Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2006-1932
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Background/Aims: Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide ( GIP). The present study asked whether vildagliptin accentuates glibenclamide-induced hypoglycemia or affects endogenous secretion of GLP-1 and GIP after an oral glucose tolerance test. Methods: There were 16 healthy male subjects studied on four occasions after an overnight fast in a double-blind, four-way crossover study. In random order, vildagliptin ( 100 mg) or placebo, with and without glibenclamide ( 5 mg), was administered 30 min before 75 g oral glucose. Blood was sampled to measure glucose, and total ( sum of active and inactive) GLP-1 and GIP. Statistical evaluation was done using repeated-measures ANOVA. Results: Glibenclamide provoked hypoglycemia (<= 1.9 mM), but this was not accentuated by the simultaneous administration of vildagliptin ( P = 0.25). The integrated incremental responses of total GLP-1 were reduced by vildagliptin by 72% ( with glibenclamide) and 48% ( without glibenclamide) ( effect of vildagliptin: P < 0.0001; glibenclamide: P = 0.31; interaction: P = 0.26). Similarly, integrated incremental responses of total GIP were reduced by vildagliptin by 26 and 21%, with and without glibenclamide, respectively ( vildagliptin: P = 0.017; glibenclamide: P = 0.44; interaction: P = 0.69). Conclusions: Sulfonylurea-induced hypoglycemia after the oral administration of glibenclamide is not accentuated by the coadministration of vildagliptin. This may be explained by a negative feedback regulation of GLP-1 and GIP secretion that limits the degree to which the active incretin levels are enhanced.
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