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

Institute of Biomedical Engineering (A.M.), National Research Council, I-35127 Padova, Italy; Department of Endocrinology, Diabetes, and Rheumatology (W.A.S.), University Hospital Duesseldorf, D-40225 Duesseldorf, Germany; University Hospital (P.M.N.), 205 02 Malmö, Sweden; Medical Group (G.L.), 40000 Mont de Marsan, France; Novartis Pharma AG (A.S.), CH-4056 Basel, Switzerland; PharmaWrite (B.E.D.), Princeton, New Jersey 08540; and Novartis Pharmaceuticals Corporation (S.J., J.E.F.), East Hanover, New Jersey 07936

Address all correspondence and requests for reprints to: Andrea Mari, Ph.D., ISIB-CNR, Corso Stati Uniti 4, 35127 Padova, Italy. E-mail: andrea.mari{at}isib.cnr.it.

Objective: This study was conducted to characterize the effects of vildagliptin on β-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 β-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 pmol·min^–1·m^–2, P < 0.001] glucose sensitivity (AM = +20.7 ± 5.2 pmol·min^–1·m^–2·mM^–1, P < 0.001), and rate sensitivity (AM = +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 β-cell function were accompanied by a decrease in the glucose area under the curve at 0–2 h (AM = –1.7 ± 0.5 mM/h, P = 0.002) and in glycosylated hemoglobin (AM = –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 β-cell function is maintained throughout 52-wk treatment with vildagliptin and underlies a sustained improvement in glycemic control. However, no effects remain after washout.

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