Characterization of the Influence of Vildagliptin on Model-Assessed b-Cell Function in Patients with Type 2 Diabetes and Mild Hyperglycemia

Objective: This study was conducted to characterize the effects of vildagliptin on -cell function in patients with type 2 diabetes and mild hyperglycemia. Design: A 52-wk double-blind, randomized, parallel-group study comparing vildagliptin (50 mg every day) and placebo was conducted in 306 patients with mild hyperglycemia (glycosylated hemoglobin of 6.2-7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline,wk24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and -cell function was quantified with a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor. Results: Vildagliptin significantly increased fasting insulin secretory tone [between-group difference in adjusted mean change from baseline to wk 52 (AM)34.1 9.5 pmolmin1m2, P 0.001] glucose sensitivity (AM 20.7 5.2 pmolmin1m2mM1, P 0.001), and rate sensitivity (AM163.667.0 pmolm2mM1, P0.015), but total insulin secretion (ISR area under the curve at 0-2 h) and the potentiation factor excursion during meals were unchanged. These improvements in -cell function were accompanied by a decrease in the glucose area under the curve at 0-2 h (AM1.70.5mM/h, P0.002) and in glycosylated hemoglobin (AM0.3 0.1%, P 0.001). None of the effects of vildagliptin remained after 4-wk washout from study medication. Conclusions: Consistent with previous findings from shorter-term studies in patients with more severe hyperglycemia, in patients with mild hyperglycemia, improved -cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.