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Evidence that vildagliptin attenuates deterioration of glycaemic control during 2‐year treatment of patients with type 2 diabetes and mild hyperglycaemia *
Author(s) -
Scherbaum W. A.,
Schweizer A.,
Mari A.,
Nilsson P. M.,
Lalanne G.,
Wang Y.,
Dunning B. E.,
Foley J. E.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2008.00875.x
Subject(s) - vildagliptin , medicine , tolerability , postprandial , placebo , type 2 diabetes , washout , diabetes mellitus , area under the curve , insulin , gastroenterology , endocrinology , adverse effect , alternative medicine , pathology
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 (HbA 1c ) 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 (AUC 0–2 h )/insulin secretory rate (ISR) AUC 0–2 h (ISR/G). Changes from baseline and between‐treatment differences (placebo‐adjusted changes from baseline during vildagliptin treatment) were analysed by ancova . Results: The placebo‐adjusted change from week 0 in HbA 1c 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 AUC 0–2 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/m 2 /mM (p = 0.058) and the placebo‐adjusted difference in the change from week 0 to week 112 in HbA 1c 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.