Advanced

Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes.

Farngren, Johan LU ; Persson, Margaretha LU ; Schweizer, Anja; Foley, James E and Ahrén, Bo LU (2012) In The Journal of clinical endocrinology and metabolism 97(10). p.3799-3806
Abstract
Context:

The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.Objective:The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).



Patients and Methods:

The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28... (More)
Context:

The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.Objective:The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).



Patients and Methods:

The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.



Main Outcome Measure:

The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured.Results:During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4 ± 1.0 mmol/mol (-0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%).



Conclusions:

Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of clinical endocrinology and metabolism
volume
97
issue
10
pages
3799 - 3806
publisher
The Endocrine Society
external identifiers
  • wos:000309664400079
  • pmid:22855332
  • scopus:84867238377
ISSN
1945-7197
DOI
10.1210/jc.2012-2332
language
English
LU publication?
yes
id
2209f45f-eefb-45b6-87dd-a110f83acd09 (old id 3047832)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22855332?dopt=Abstract
date added to LUP
2012-09-04 20:52:27
date last changed
2017-08-27 04:31:54
@article{2209f45f-eefb-45b6-87dd-a110f83acd09,
  abstract     = {Context:<br/><br>
The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.Objective:The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).<br/><br>
<br/><br>
Patients and Methods:<br/><br>
The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.<br/><br>
<br/><br>
Main Outcome Measure:<br/><br>
The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured.Results:During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4 ± 1.0 mmol/mol (-0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%).<br/><br>
<br/><br>
Conclusions:<br/><br>
Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.},
  author       = {Farngren, Johan and Persson, Margaretha and Schweizer, Anja and Foley, James E and Ahrén, Bo},
  issn         = {1945-7197},
  language     = {eng},
  number       = {10},
  pages        = {3799--3806},
  publisher    = {The Endocrine Society},
  series       = {The Journal of clinical endocrinology and metabolism},
  title        = {Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes.},
  url          = {http://dx.doi.org/10.1210/jc.2012-2332},
  volume       = {97},
  year         = {2012},
}