Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist.

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist. / Nauck, Michael A; Kind, J; Köthe, Lars D; Holst, Jens Juul; Deacon, Carolyn F.; Broschag, M; He, YL; Kjems, L; Foley, J.

In: Diabetes, Vol. 65, No. 8, 2016, p. 2440-2447.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Nauck, MA, Kind, J, Köthe, LD, Holst, JJ, Deacon, CF, Broschag, M, He, YL, Kjems, L & Foley, J 2016, 'Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist.', Diabetes, vol. 65, no. 8, pp. 2440-2447. https://doi.org/10.2337/db16-0107

APA

Nauck, M. A., Kind, J., Köthe, L. D., Holst, J. J., Deacon, C. F., Broschag, M., ... Foley, J. (2016). Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist. Diabetes, 65(8), 2440-2447. https://doi.org/10.2337/db16-0107

Vancouver

Nauck MA, Kind J, Köthe LD, Holst JJ, Deacon CF, Broschag M et al. Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist. Diabetes. 2016;65(8):2440-2447. https://doi.org/10.2337/db16-0107

Author

Nauck, Michael A ; Kind, J ; Köthe, Lars D ; Holst, Jens Juul ; Deacon, Carolyn F. ; Broschag, M ; He, YL ; Kjems, L ; Foley, J. / Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist. In: Diabetes. 2016 ; Vol. 65, No. 8. pp. 2440-2447.

Bibtex

@article{aaaa7c83ab294907a5f74bea883a7bdc,
title = "Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist.",
abstract = "We quantified the contribution of GLP-1 as a mediator of the therapeutic effects of dipeptidyl peptidase 4 (DPP-4) inhibition (vildagliptin) by using the GLP-1 receptor antagonist exendin [9-39] in patients with type 2 diabetes and in healthy subjects. Thirty-two patients with type 2 diabetes and 29 age-and weight-matched healthy control subjects were treated in randomized order with 100 mg once daily vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10) without and with a high-dose intravenous infusion of exendin [9-39]. The main end point was the ratio of the areas under the curve (AUCs) of integrated insulin secretion rates (total AUC(ISR)) and glucose (total AUC(glucose)) over 4 h after the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and glucose-dependent insulinotropic polypeptide and lowered glucose responses without changing AUC(ISR)/AUC(glucose) in healthy subjects. Vildagliptin significantly increased this ratio by 10.5{\%} in patients with type 2 diabetes, and exendin [9-39] reduced it (both P < 0.0001). The percentage reduction in the AUC(ISR)/AUC(glucose) ratio achieved with exendin [9-39] was significantly smaller after vildagliptin treatment than after placebo treatment (P = 0.026) and was equivalent to 47 6 5{\%} of the increments due to vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.",
author = "Nauck, {Michael A} and J Kind and K{\"o}the, {Lars D} and Holst, {Jens Juul} and Deacon, {Carolyn F.} and M Broschag and YL He and L Kjems and J. Foley",
year = "2016",
doi = "10.2337/db16-0107",
language = "English",
volume = "65",
pages = "2440--2447",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "8",

}

RIS

TY - JOUR

T1 - Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and type 2-diabetic patients using exendin [9-39] as a GLP-1 receptor antagonist.

AU - Nauck, Michael A

AU - Kind, J

AU - Köthe, Lars D

AU - Holst, Jens Juul

AU - Deacon, Carolyn F.

AU - Broschag, M

AU - He, YL

AU - Kjems, L

AU - Foley, J.

PY - 2016

Y1 - 2016

N2 - We quantified the contribution of GLP-1 as a mediator of the therapeutic effects of dipeptidyl peptidase 4 (DPP-4) inhibition (vildagliptin) by using the GLP-1 receptor antagonist exendin [9-39] in patients with type 2 diabetes and in healthy subjects. Thirty-two patients with type 2 diabetes and 29 age-and weight-matched healthy control subjects were treated in randomized order with 100 mg once daily vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10) without and with a high-dose intravenous infusion of exendin [9-39]. The main end point was the ratio of the areas under the curve (AUCs) of integrated insulin secretion rates (total AUC(ISR)) and glucose (total AUC(glucose)) over 4 h after the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and glucose-dependent insulinotropic polypeptide and lowered glucose responses without changing AUC(ISR)/AUC(glucose) in healthy subjects. Vildagliptin significantly increased this ratio by 10.5% in patients with type 2 diabetes, and exendin [9-39] reduced it (both P < 0.0001). The percentage reduction in the AUC(ISR)/AUC(glucose) ratio achieved with exendin [9-39] was significantly smaller after vildagliptin treatment than after placebo treatment (P = 0.026) and was equivalent to 47 6 5% of the increments due to vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.

AB - We quantified the contribution of GLP-1 as a mediator of the therapeutic effects of dipeptidyl peptidase 4 (DPP-4) inhibition (vildagliptin) by using the GLP-1 receptor antagonist exendin [9-39] in patients with type 2 diabetes and in healthy subjects. Thirty-two patients with type 2 diabetes and 29 age-and weight-matched healthy control subjects were treated in randomized order with 100 mg once daily vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10) without and with a high-dose intravenous infusion of exendin [9-39]. The main end point was the ratio of the areas under the curve (AUCs) of integrated insulin secretion rates (total AUC(ISR)) and glucose (total AUC(glucose)) over 4 h after the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and glucose-dependent insulinotropic polypeptide and lowered glucose responses without changing AUC(ISR)/AUC(glucose) in healthy subjects. Vildagliptin significantly increased this ratio by 10.5% in patients with type 2 diabetes, and exendin [9-39] reduced it (both P < 0.0001). The percentage reduction in the AUC(ISR)/AUC(glucose) ratio achieved with exendin [9-39] was significantly smaller after vildagliptin treatment than after placebo treatment (P = 0.026) and was equivalent to 47 6 5% of the increments due to vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.

U2 - 10.2337/db16-0107

DO - 10.2337/db16-0107

M3 - Journal article

C2 - 27207543

VL - 65

SP - 2440

EP - 2447

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 8

ER -

ID: 162894252