PMID- 28408838
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20221207
IS  - 1178-2048 (Electronic)
IS  - 1176-6344 (Print)
IS  - 1176-6344 (Linking)
VI  - 13
DP  - 2017
TI  - DPP-4 inhibitor treatment: beta-cell response but not HbA(1c) reduction is dependent 
      on the duration of diabetes.
PG  - 123-126
LID - 10.2147/VHRM.S125850 [doi]
AB  - INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in 
      patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and 
      suppressing glucagon secretion. Since T2DM is associated with progressive loss of 
      beta-cell function, we hypothesized that the DPP-4 inhibitor action to improve 
      beta-cell function would be attenuated with longer duration of T2DM. METHODS: Data 
      from six randomized, placebo-controlled trials of 24 weeks duration, where beta-cell 
      response to vildagliptin 50 mg twice daily was assessed, were pooled. In each 
      study, the insulin secretory rate relative to glucose (ISR/G 0-2h) during glucose 
      load (standard meal or oral glucose tolerance test) was assessed at baseline and 
      end of study. The mean placebo-subtracted difference (PSD) in the change in ISR/G 
      0-2h from baseline for each study was evaluated as a function of age, duration of 
      T2DM, baseline ISR/G 0-2h, glycated hemoglobin (HbA(1c)), fasting plasma glucose, 
      body mass index, and mean PSD in the change in HbA(1c) from baseline, using 
      univariate model. RESULTS: There was a strong negative association between the 
      PSD in the change from baseline in ISR/G 0-2h and duration of T2DM (r= -0.89, 
      p<0.02). However, there was no association between the PSD in the change from 
      baseline in ISR/G 0-2h and the PSD in the change from baseline in HbA(1c) 
      (r=0.33, p=0.52). None of the other characteristics were significantly associated 
      with mean PSD change in ISR/G 0-2h. CONCLUSION: These findings indicate that the 
      response of the beta-cell, but not the HbA(1c) reduction, with vildagliptin is 
      dependent on duration of T2DM. Further, it can be speculated that glucagon 
      suppression may become the predominant mechanism via which glycemic control is 
      improved when treatment with a DPP-4 inhibitor, such as vildagliptin, is 
      initiated late in the natural course of T2DM.
FAU - Kozlovski, Plamen
AU  - Kozlovski P
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Bhosekar, Vaishali
AU  - Bhosekar V
AD  - Novartis Healthcare Private Limited, Hyderabad, India.
FAU - Foley, James E
AU  - Foley JE
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
LA  - eng
PT  - Journal Article
PT  - Video-Audio Media
DEP - 20170331
PL  - New Zealand
TA  - Vasc Health Risk Manag
JT  - Vascular health and risk management
JID - 101273479
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidines)
RN  - 0 (hemoglobin A1c protein, human)
RN  - EC 3.4.14.5 (DPP4 protein, human)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
RN  - I6B4B2U96P (Vildagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/adverse effects/*analogs & derivatives/therapeutic use
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Blood Glucose/*drug effects/metabolism
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/enzymology
MH  - Dipeptidyl Peptidase 4/*metabolism
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use
MH  - Female
MH  - Glycated Hemoglobin/*metabolism
MH  - Humans
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Nitriles/adverse effects/*therapeutic use
MH  - Pyrrolidines/adverse effects/*therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vildagliptin
PMC - PMC5383079
OTO - NOTNLM
OT  - gastric inhibitory polypeptide
OT  - glucagon
OT  - glucagon-like peptide 1
OT  - insulin
OT  - insulin secretion rate
OT  - alpha-cell
OT  - beta-cell
COIS- Disclosure PK and JEF are employed by and own stocks in Novartis. VB is employed 
      by Novartis. The study was funded by Novartis Pharma AG. Part of this data was 
      presented as a poster (1093-P) at the 76th Scientific Sessions of the American 
      Diabetes Association, June 10-14, 2016, New Orleans, LA, USA. The authors report 
      no other conflicts of interest in this work.
EDAT- 2017/04/15 06:00
MHDA- 2017/08/02 06:00
PMCR- 2017/03/31
CRDT- 2017/04/15 06:00
PHST- 2017/04/15 06:00 [entrez]
PHST- 2017/04/15 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/03/31 00:00 [pmc-release]
AID - vhrm-13-123 [pii]
AID - 10.2147/VHRM.S125850 [doi]
PST - epublish
SO  - Vasc Health Risk Manag. 2017 Mar 31;13:123-126. doi: 10.2147/VHRM.S125850. 
      eCollection 2017.