Vildagliptin, a Dipeptidyl Peptidase-IV Inhibitor, Improves Model-Assessed β-Cell Function in Patients with Type 2 Diabetes

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Abstract
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 β-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 β-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (β-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 (ΔLSM) was 101 ± 51 pmol·min−1·m−2 (P = 0.002). The slope of the β-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (ΔLSM, −1.2 ± 0.4 mmol/liter; P = 0.01) and glucagon (ΔLSM, −10.7 ± 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (ΔLSM, +10.8 ± 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (ΔLSM, +43.4 ± 9.4 pmol/liter; P < 0.0001) relative to placebo. Conclusion: Vildagliptin is an incretin degradation inhibitor that improves β-cell function in diabetic patients by increasing the insulin secretory tone.

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