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Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance

Rosenstock, J; Foley, J E; Rendell, M; Landin-Olsson, Mona LU ; Holst, J J; Deacon, C F; Rochotte, E and Baron, M A (2008) In Diabetes Care 31(1). p.30-35
Abstract
Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to... (More)
Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental (Delta) AUC(0-2h) for these analytes were assessed by ANCOVA; glucose AUC(0-2h) was the primary outcome variable. Results: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0+/-1.2 pmol/l*h, P<0.001) and GIP (DeltaAUC, +46.8+/-5.4 pmol/l*h, P<0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol/l*h, P=0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8+/-35.7 pmol/l*h, P=0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0+/-0.3 mmol/l*h, P<0.001), representing approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2h)/glucose AUC(0-2h) was significantly increased (+6.4 +/- 2.0 pmol*min(-1)*m(-2)*mM(-1), P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported. Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
31
issue
1
pages
30 - 35
publisher
American Diabetes Association
external identifiers
  • pmid:17947341
  • wos:000252178900007
  • scopus:38149096290
ISSN
1935-5548
DOI
10.2337/dc07-1616
language
English
LU publication?
yes
id
45106413-6b59-4525-9ffd-390f22fec90b (old id 1143111)
date added to LUP
2008-07-31 12:13:18
date last changed
2017-09-03 04:24:50
@article{45106413-6b59-4525-9ffd-390f22fec90b,
  abstract     = {Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental (Delta) AUC(0-2h) for these analytes were assessed by ANCOVA; glucose AUC(0-2h) was the primary outcome variable. Results: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0+/-1.2 pmol/l*h, P&lt;0.001) and GIP (DeltaAUC, +46.8+/-5.4 pmol/l*h, P&lt;0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol/l*h, P=0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8+/-35.7 pmol/l*h, P=0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0+/-0.3 mmol/l*h, P&lt;0.001), representing approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2h)/glucose AUC(0-2h) was significantly increased (+6.4 +/- 2.0 pmol*min(-1)*m(-2)*mM(-1), P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported. Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.},
  author       = {Rosenstock, J and Foley, J E and Rendell, M and Landin-Olsson, Mona and Holst, J J and Deacon, C F and Rochotte, E and Baron, M A},
  issn         = {1935-5548},
  language     = {eng},
  number       = {1},
  pages        = {30--35},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance},
  url          = {http://dx.doi.org/10.2337/dc07-1616},
  volume       = {31},
  year         = {2008},
}