The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion
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The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. / El-Ouaghlidi, Andrea; Rehring, Erika; Holst, Jens Juul; Schweizer, Anja; Foley, James; Holmes, David; Nauck, Michael A.
In: The Journal of clinical endocrinology and metabolism, Vol. 92, No. 11, 11.2007, p. 4165-71.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion
AU - El-Ouaghlidi, Andrea
AU - Rehring, Erika
AU - Holst, Jens Juul
AU - Schweizer, Anja
AU - Foley, James
AU - Holmes, David
AU - Nauck, Michael A
PY - 2007/11
Y1 - 2007/11
N2 - 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 (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.
AB - 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 (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.
KW - Adamantane
KW - Adult
KW - Algorithms
KW - C-Peptide
KW - Dipeptidyl-Peptidase IV Inhibitors
KW - Drug Interactions
KW - Enzyme-Linked Immunosorbent Assay
KW - Gastric Emptying
KW - Gastric Inhibitory Polypeptide
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Glucose
KW - Glyburide
KW - Humans
KW - Hydrocortisone
KW - Hypoglycemia
KW - Hypoglycemic Agents
KW - Insulin
KW - Male
KW - Nitriles
KW - Pyrrolidines
U2 - 10.1210/jc.2006-1932
DO - 10.1210/jc.2006-1932
M3 - Journal article
C2 - 17698900
VL - 92
SP - 4165
EP - 4171
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -
ID: 132049840