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Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes.

Ahrén, Bo LU ; Schweizer, Anja; Dejager, Sylvie; Dunning, Beth E; Nilsson, Peter LU ; Persson, Margaretha LU and Foley, James E (2009) In Journal of Clinical Endocrinology and Metabolism 94. p.1236-1243
Abstract
Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c </=7.5% Intervention: Vildagliptin (100 mg qd) or placebo Primary Outcome... (More)
Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c </=7.5% Intervention: Vildagliptin (100 mg qd) or placebo Primary Outcome Measure(s): 1) Change in plasma glucagon levels during hypoglycemic (2.5 mM glucose) clamp. 2) Incremental (Delta) glucagon area under the concentration-time curve from time 0 to 60 min (AUC0-60min) during standard meal test. Before the study, it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia. Results: The mean change in glucagon during hypoglycemic clamp was 46.7+/-6.9 ng/liter with vildagliptin treatment and 33.9+/-6.7 ng/liter with placebo; the between-treatment difference was 12.8+/-7.0 ng/liter (P=0.039), representing a 38% increase with vildagliptin. In contrast, the mean glucagon DeltaAUC0-60min during meal test with vildagliptin was 512+/-163 ng/liter.min vs 861+/-130 ng/liter.min with placebo; the between-treatment difference was -349+/-158 ng/liter.min (P=0.019), representing a 41% decrease with vildagliptin. Conclusions: Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects of hyperglycemia and the stimulatory effects of hypoglycemia. These effects likely contribute to the efficacy of vildagliptin to improve glycemic control as well as to its low hypoglycemic potential. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
94
pages
1236 - 1243
publisher
The Endocrine Society
external identifiers
  • wos:000265145100030
  • pmid:19174497
  • scopus:65249095686
ISSN
1945-7197
DOI
10.1210/jc.2008-2152
language
English
LU publication?
yes
id
8a9e2724-58ed-4384-b529-17dd2e765b45 (old id 1289209)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19174497?dopt=Abstract
date added to LUP
2009-02-03 12:26:27
date last changed
2017-11-05 04:45:45
@article{8a9e2724-58ed-4384-b529-17dd2e765b45,
  abstract     = {Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c &lt;/=7.5% Intervention: Vildagliptin (100 mg qd) or placebo Primary Outcome Measure(s): 1) Change in plasma glucagon levels during hypoglycemic (2.5 mM glucose) clamp. 2) Incremental (Delta) glucagon area under the concentration-time curve from time 0 to 60 min (AUC0-60min) during standard meal test. Before the study, it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia. Results: The mean change in glucagon during hypoglycemic clamp was 46.7+/-6.9 ng/liter with vildagliptin treatment and 33.9+/-6.7 ng/liter with placebo; the between-treatment difference was 12.8+/-7.0 ng/liter (P=0.039), representing a 38% increase with vildagliptin. In contrast, the mean glucagon DeltaAUC0-60min during meal test with vildagliptin was 512+/-163 ng/liter.min vs 861+/-130 ng/liter.min with placebo; the between-treatment difference was -349+/-158 ng/liter.min (P=0.019), representing a 41% decrease with vildagliptin. Conclusions: Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects of hyperglycemia and the stimulatory effects of hypoglycemia. These effects likely contribute to the efficacy of vildagliptin to improve glycemic control as well as to its low hypoglycemic potential.},
  author       = {Ahrén, Bo and Schweizer, Anja and Dejager, Sylvie and Dunning, Beth E and Nilsson, Peter and Persson, Margaretha and Foley, James E},
  issn         = {1945-7197},
  language     = {eng},
  pages        = {1236--1243},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes.},
  url          = {http://dx.doi.org/10.1210/jc.2008-2152},
  volume       = {94},
  year         = {2009},
}