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National Research Center, Institute of Biomedical Engineering (A.M.), Padova, Italy; Novartis Pharmaceuticals Corp. (W.M.S., M.L.-S., J.E.F.), East Hanover, New Jersey 07936; Novartis Institutes for Biomedical Research (Y.L.H., C.W.), Cambridge, Massachusetts 02139; PharmaWrite, LLC (B.E.D.), Princeton, NJ 08540; and Panum Institute, University of Copenhagen (C.F.D., J.J.H.), Copenhagen, Denmark
Address all correspondence and requests for reprints to: Dr. Andrea Mari, National Research Center, Institute of Biomedical Engineering, Corso Stati Uniti 4, 35127 Padova, Italy. E-mail: andrea.mari{at}isib.cnr.it.
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 ß-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 ß-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (ß-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 (
LSM) was 101 ± 51 pmol·min–1·m–2 (P = 0.002). The slope of the ß-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (LSM, –1.2 ± 0.4 mmol/liter; P = 0.01) and glucagon (LSM, –10.7 ± 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (LSM, +10.8 ± 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (LSM, +43.4 ± 9.4 pmol/liter; P < 0.0001) relative to placebo.
Conclusion: Vildagliptin is an incretin degradation inhibitor that improves ß-cell function in diabetic patients by increasing the insulin secretory tone.
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