Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes

TY - JOUR

T1 - Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes

AU - Mari, A

AU - Sallas, W M

AU - He, Y L

AU - Watson, C

AU - Ligueros-Saylan, M

AU - Dunning, B E

AU - Deacon, C F

AU - Holst, Jens Juul

AU - Foley, J E

PY - 2005/8

Y1 - 2005/8

N2 - AIMS/HYPOTHESIS: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function.METHODS: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors.RESULTS: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo.CONCLUSION: Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.

AB - AIMS/HYPOTHESIS: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function.METHODS: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors.RESULTS: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo.CONCLUSION: Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.

KW - Adamantane

KW - Adenosine Deaminase Inhibitors

KW - Adult

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 2

KW - Dipeptidyl Peptidase 4

KW - Enzyme Inhibitors

KW - Female

KW - Glycoproteins

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Male

KW - Middle Aged

KW - Models, Biological

KW - Nitriles

KW - Pyrrolidines

KW - Treatment Outcome

U2 - 10.1210/jc.2004-2460

DO - 10.1210/jc.2004-2460

M3 - Journal article

C2 - 15886245

SN - 0021-972X

VL - 90

SP - 4888

EP - 4894

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -