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

作者：Andrea Mari, William M. Sallas, Yanling He, C. E. Watson, Monica Ligueros‐Saylan, Beth E. Dunning, Carolyn F. Deacon, Jens J. Holst, James E. Foley · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2005 · DOI：10.1210/jc.2004-2460 · 被引用次数：362 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Diabetes and associated disorders

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 inta...