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Aim: To assess the 2-year efficacy and tolerability of vildagliptin (50 mg once daily) in patients with type 2 diabetes (T2DM) and mild hyperglycaemia. Methods: This was a multicentre, randomized, double-blind, placebo-controlled trial comprising a 52-week core study with a 4-week, active treatment–free washout followed by a 52-week extension study with another washout period conducted in 131 drug-naïve patients with T2DM and mild hyperglycaemia [glycosylated haemoglobin (HbA1c) 6.2–7.2%]. All patients received lifestyle counselling at each study visit. Efficacy and tolerability were assessed during visits at weeks 0 (core study baseline), 4, 8, 12, 16, 24, 32, 40 and 52 of active treatment; at week 56 (i.e. after the first washout period); at weeks 68, 80, 96 and 108 and at week 112 (i.e. after the second washout period). Standard meal tests were also performed at weeks 0, 24, 52, 56, 80, 108 and 112 to assess postprandial glycaemia and β-cell function, which was quantified by glucose area under the curve (AUC0–2 h (ISR/G). Changes from baseline and between-treatment differences (placebo-adjusted changes from baseline during vildagliptin treatment) were analysed byancova. Results: The placebo-adjusted change from week 0 in HbA0–2 h and in the β-cell function parameter, ISR/G, tended to be greater after 2 years than after 1 year of treatment with vildagliptin. Even after a 4-week washout, the placebo-adjusted change from week 0 to week 112 in ISR/G was 3.2 ± 1.6 pmol/min/m1c was −0.3 ± 0.1% after 1 year of vildagliptin treatment (p < 0.001) and −0.5 ± 0.2% after 2 years (p = 0.008). The placebo-adjusted change from core study baseline in fasting plasma glucose, in glucose AUC0–2 was −0.3 ± 0.1% (p = 0.051). The incidences of adverse events (AEs), serious AEs and discontinuations because of AEs were similar in the two treatment groups, and hypoglycaemic episodes were reported by no patient receiving vildagliptin and by two patients receiving placebo. Conclusions: In drug-naïve patients with mild hyperglycaemia, 2-year treatment with vildagliptin 50 mg once daily attenuated the progressive loss of glycaemic control seen in patients receiving only lifestyle counselling (and placebo). This appears to be because of a corresponding attenuation of the deterioration of β-cell function as assessed by ISR/G. [ABSTRACT FROM AUTHOR]h and in the β-cell function parameter, ISR/G, tended to be greater after 2 years than after 1 year of treatment with vildagliptin. Even after a 4-week washout, the placebo-adjusted change from week 0 to week 112 in ISR/G was 3.2 ± 1.6 pmol/min/m2/mM (p = 0.058) and the placebo-adjusted difference in the change from week 0 to week 112 in HbA1c was −0.3 ± 0.1% (p = 0.051). The incidences of adverse events (AEs), serious AEs and discontinuations because of AEs were similar in the two treatment groups, and hypoglycaemic episodes were reported by no patient receiving vildagliptin and by two patients receiving placebo. Conclusions: In drug-naïve patients with mild hyperglycaemia, 2-year treatment with vildagliptin 50 mg once daily attenuated the progressive loss of glycaemic control seen in patients receiving only lifestyle counselling (and placebo). This appears to be because of a corresponding attenuation of the deterioration of β-cell function as assessed by ISR/G. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to assess efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia. Methods: Multicentre, double-blind, randomized, placebo-controlled, parallel-group study of 52-week treatment with vildagliptin (50 mg q.d.) in 306 drug-naïve patients with type 2 diabetes (A1C = 6.2–7.5%). A1C, fasting plasma glucose (FPG) and measures of prandial glucose control and beta-cell function determined during standard meal tests were assessed. Results: Baseline A1C and FPG averaged 6.7% and 7.1 mmol/l, respectively, in patients randomized to vildagliptin (n = 156) and 6.8% and 7.2 mmol/l in those randomized to placebo (n = 150). A1C decreased modestly in vildagliptin-treated patients (Δ = −0.2 ± 0.1%) and increased in patients receiving placebo (Δ = 0.1 ± 0.1%). The between-group difference (vildagliptin − placebo) in adjusted mean change (AMΔ) in A1C was −0.3 ± 0.1% (p < 0.001). FPG increased in patients receiving placebo (Δ = 0.5 ± 0.1 mmol/l) and to a significantly lesser extent in vildagliptin-treated patients (between-group difference in AMΔ FPG = −0.4 ± 0.2 mmol/l, p = 0.032). Relative to placebo, 2-h postprandial glucose (PPG) decreased (−0.9 ± 0.4 mmol/l, p = 0.012), and insulin secretory rate (ISR) relative to glucose [ISR area under the curve (AUC)0–2 h/glucose AUC0–2 h] increased (+5.0 ± 1.2 pmol/min/m2/mM, p < 0.001). Mean body weight decreased by 0.5 ± 0.3 kg in vildagliptin-treated patients and by 0.2 ± 0.3 kg in patients receiving placebo. The side-effect profile of vildagliptin was similar to that of placebo, and one hypoglycaemic episode occurred in one patient receiving placebo. Conclusions: In drug-naïve patients with mild hyperglycaemia, relative to placebo, 52-week treatment with vildagliptin 50 mg q.d. significantly decreases A1C, FPG and PPG and improves beta-cell function without weight gain or hypoglycaemia. [ABSTRACT FROM AUTHOR]