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

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 -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 -cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (-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 pmolmin1m2 (P0.002). The slope of the -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 -cell function in diabetic patients by increasing the insulin secretory tone