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

• 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 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 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 [Delta]= +34.1 +/- 9.5 pmol*min(-1) *m(-2), P<0.001) glucose sensitivity (Delta= +20.7 +/- 5.2 pmol*min(-1) *m(-2) *mM(-1), P < 0.001) and rate sensitivity (Delta= +163.6 +/- 67.0 pmol*m(-2) *mM(-1), P = 0.015) but total insulin secretion (ISR AUC0-2h) and the potentiation factor excursion during meals were unchanged. These improvements in beta-cell function were accompanied by a decrease in the glucose AUC0-2h (Delta = -1.7 +/- 0.5 mM*h, P = 0.002) and in A1C (Delta = -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 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)

Nyckelord

GIP

GLP-1

incretin

insulin secretion

dipeptidyl peptidase-IV

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)