PMID- 18355325
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 10
IP  - 11
DP  - 2008 Nov
TI  - Evidence that vildagliptin attenuates deterioration of glycaemic control during 
      2-year treatment of patients with type 2 diabetes and mild hyperglycaemia.
PG  - 1114-24
LID - 10.1111/j.1463-1326.2008.00875.x [doi]
AB  - 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-naive 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 beta-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 beta-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-naive 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 beta-cell function as assessed 
      by ISR/G.
FAU - Scherbaum, W A
AU  - Scherbaum WA
AD  - Department of Endocrinology, Diabetes and Rheumatology, University Hospital 
      Dusseldorf, Dusseldorf, Germany.
FAU - Schweizer, A
AU  - Schweizer A
FAU - Mari, A
AU  - Mari A
FAU - Nilsson, P M
AU  - Nilsson PM
FAU - Lalanne, G
AU  - Lalanne G
FAU - Wang, Y
AU  - Wang Y
FAU - Dunning, B E
AU  - Dunning BE
FAU - Foley, J E
AU  - Foley JE
LA  - eng
SI  - ClinicalTrials.gov/NCT00300287
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080318
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Insulin)
RN  - 0 (Lipids)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidines)
RN  - I6B4B2U96P (Vildagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/therapeutic use
MH  - Adult
MH  - Analysis of Variance
MH  - Blood Glucose/analysis
MH  - Body Weight
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hyperglycemia/blood/*drug therapy
MH  - Insulin/blood
MH  - Lipids/blood
MH  - Male
MH  - Middle Aged
MH  - Nitriles/*therapeutic use
MH  - Postprandial Period
MH  - Pyrrolidines/*therapeutic use
MH  - Time Factors
MH  - Vildagliptin
EDAT- 2008/03/22 09:00
MHDA- 2009/08/21 09:00
CRDT- 2008/03/22 09:00
PHST- 2008/03/22 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
PHST- 2008/03/22 09:00 [entrez]
AID - DOM875 [pii]
AID - 10.1111/j.1463-1326.2008.00875.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2008 Nov;10(11):1114-24. doi: 
      10.1111/j.1463-1326.2008.00875.x. Epub 2008 Mar 18.