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:
https://lup.lub.lu.se/record/3047832
- author
- Farngren, Johan
LU
; Persson, Margaretha
LU
; Schweizer, Anja
; Foley, James E
and Ahrén, Bo
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of clinical endocrinology and metabolism
- volume
- 97
- issue
- 10
- pages
- 3799 - 3806
- publisher
- Oxford University Press
- external identifiers
-
- wos:000309664400079
- pmid:22855332
- scopus:84867238377
- pmid:22855332
- 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
- 2016-04-01 13:05:00
- date last changed
- 2024-01-09 07:03:05
@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 = {{Oxford University Press}},
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 = {{https://lup.lub.lu.se/search/files/3148139/3126694.pdf}},
doi = {{10.1210/jc.2012-2332}},
volume = {{97}},
year = {{2012}},
}