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Characterization of the Influence of Vildagliptin on Model-Assessed {beta}-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia.

Mari, Andrea; Scherbaum, Werner A; Nilsson, Peter LU ; Lalanne, Gerard; Schweizer, Anja; Dunning, Beth E; Jauffret, Sophie and Foley, James E (2009) In Journal of Clinical Endocrinology and Metabolism 93(1). p.103-109
Abstract
Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change... (More)
Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone (between-group difference in adjusted mean change from baseline to wk 52 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P<0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P < 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -0.3 +/- 0.1%, P < 0.001). None of the effects of vildagliptin remained following 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GIP, GLP-1, incretin, insulin secretion, dipeptidyl peptidase-IV
in
Journal of Clinical Endocrinology and Metabolism
volume
93
issue
1
pages
103 - 109
publisher
The Endocrine Society
external identifiers
  • scopus:38149137991
  • pmid:17925336
  • wos:000252359400020
ISSN
1945-7197
DOI
10.1210/jc.2007-1639
language
English
LU publication?
yes
id
47e91364-8dbb-4559-a6ba-0b4e40cd2fca (old id 608691)
date added to LUP
2008-08-15 09:30:19
date last changed
2017-09-03 04:08:27
@article{47e91364-8dbb-4559-a6ba-0b4e40cd2fca,
  abstract     = {Objective: This study was conducted to characterize the effects of vildagliptin on beta-cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution and beta-cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone (between-group difference in adjusted mean change from baseline to wk 52 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P&lt;0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P &lt; 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -0.3 +/- 0.1%, P &lt; 0.001). None of the effects of vildagliptin remained following 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.},
  author       = {Mari, Andrea and Scherbaum, Werner A and Nilsson, Peter and Lalanne, Gerard and Schweizer, Anja and Dunning, Beth E and Jauffret, Sophie and Foley, James E},
  issn         = {1945-7197},
  keyword      = {GIP,GLP-1,incretin,insulin secretion,dipeptidyl peptidase-IV},
  language     = {eng},
  number       = {1},
  pages        = {103--109},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Characterization of the Influence of Vildagliptin on Model-Assessed {beta}-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia.},
  url          = {http://dx.doi.org/10.1210/jc.2007-1639},
  volume       = {93},
  year         = {2009},
}