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 qd) and placebo was conducted in 306 patients with mild hyperglycemia (A1C = 6.2–7.5%). Plasma glucose and C-peptide levels were measured during standard meal tests performed at baseline, wk 24 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 []= +34.1 ± 9.5 pmol•min^-1 •m^-2, P<0.001) glucose sensitivity (= +20.7 ± 5.2 pmol•min^-1 •m^-2 •mM^-1, P < 0.001) and rate sensitivity (= +163.6 ± 67.0 pmol•m^-2 •mM^-1, P = 0.015) but total insulin secretion (ISR AUC_0–2h) and the potentiation factor excursion during meals were unchanged. These improvements in -cell function were accompanied by a decrease in the glucose AUC_0–2h ( = -1.7 ± 0.5 mM•h, P = 0.002) and in A1C ( = -0.3 ± 0.1%, P < 0.001). None of the effects of vildagliptin remained following 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.