Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.

Research output: Contribution to journalReview article

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Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man. / Ahrén, Bo; Schweizer, A.; Dejager, S.; Villhauer, E. B.; Dunning, B. E.; Foley, J. E.

In: Diabetes, Obesity and Metabolism, Vol. 13, No. 9, 2011, p. 775-783.

Research output: Contribution to journalReview article

Harvard

Ahrén, B, Schweizer, A, Dejager, S, Villhauer, EB, Dunning, BE & Foley, JE 2011, 'Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.', Diabetes, Obesity and Metabolism, vol. 13, no. 9, pp. 775-783. https://doi.org/10.1111/j.1463-1326.2011.01414.x

APA

Ahrén, B., Schweizer, A., Dejager, S., Villhauer, E. B., Dunning, B. E., & Foley, J. E. (2011). Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man. Diabetes, Obesity and Metabolism, 13(9), 775-783. https://doi.org/10.1111/j.1463-1326.2011.01414.x

CBE

MLA

Vancouver

Author

Ahrén, Bo ; Schweizer, A. ; Dejager, S. ; Villhauer, E. B. ; Dunning, B. E. ; Foley, J. E. / Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man. In: Diabetes, Obesity and Metabolism. 2011 ; Vol. 13, No. 9. pp. 775-783.

RIS

TY - JOUR

T1 - Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.

AU - Ahrén, Bo

AU - Schweizer, A.

AU - Dejager, S.

AU - Villhauer, E. B.

AU - Dunning, B. E.

AU - Foley, J. E.

PY - 2011

Y1 - 2011

N2 - Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.

AB - Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.

KW - dipeptidyl peptidase-4

KW - glucagon-like peptide-1

KW - glucose-dependent

KW - insulinotropic polypeptide

KW - hypoglycaemia

KW - insulin resistance

KW - islet

KW - function

KW - type 2 diabetes mellitus

U2 - 10.1111/j.1463-1326.2011.01414.x

DO - 10.1111/j.1463-1326.2011.01414.x

M3 - Review article

VL - 13

SP - 775

EP - 783

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 9

ER -