Objective: This study was conducted to characterize the effects of vildagliptin on beta-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, wk 24 and 52, and after 4-wk washout. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and beta-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 Delta) = +34.1 +/- 9.5 pmol.min(-1).m(-2), P < 0.001] glucose sensitivity (AM Delta = +20.7 +/- 5.2 pmol.min(-1).m(-2).mm(-1), P < 0.001), and rate sensitivity (AM Delta = +163.6 +/- 67.0 pmol.m(-2).mm(-1), P = 0.015), 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 beta-cell function were accompanied by a decrease in the glucose area under the curve at 0-2 h (AM Delta = -1.7 +/- 0.5 mm/h, P = 0.002) and in glycosylated hemoglobin (AM Delta = -0.3 +/- 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 beta-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.
Trial registration: ClinicalTrials.gov NCT00101712.