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.

Abstract

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 (<or=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.

• Authors: Andrea El-Ouaghlidi, Erika Rehring, Jens J Holst, Anja Schweizer, James Foley, David Holmes, Michael A Nauck
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 11 Pg. 4165-71 (Nov 2007) ISSN: 0021-972X [Print] United States
• PMID: 17698900 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• C-Peptide
• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Insulin
• Nitriles
• Pyrrolidines
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Glucagon
• Vildagliptin
• Glucose
• Adamantane
• Glyburide
• Hydrocortisone

Topics

• Adamantane (adverse effects, analogs & derivatives)
• Adult
• Algorithms
• C-Peptide (blood)
• Dipeptidyl-Peptidase IV Inhibitors (adverse effects)
• Drug Interactions
• Enzyme-Linked Immunosorbent Assay
• Gastric Emptying (drug effects)
• Gastric Inhibitory Polypeptide (antagonists & inhibitors, blood)
• Glucagon (blood)
• Glucagon-Like Peptide 1 (antagonists & inhibitors, blood)
• Glucose (pharmacology)
• Glyburide (adverse effects)
• Humans
• Hydrocortisone (blood)
• Hypoglycemia (blood, chemically induced)
• Hypoglycemic Agents (adverse effects)
• Insulin (blood)
• Male
• Nitriles (adverse effects)
• Pyrrolidines (adverse effects)
• Vildagliptin