PMID- 25858071
OWN - NLM
STAT- MEDLINE
DCOM- 20150611
LR  - 20240322
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 116
IP  - 8
DP  - 2015 Apr 10
TI  - DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical 
      trials of DPP4 inhibition.
PG  - 1491-504
LID - 10.1161/CIRCRESAHA.116.305665 [doi]
AB  - The discovery of incretin-based medications represents a major therapeutic 
      advance in the pharmacological management of type 2 diabetes mellitus (T2DM), as 
      these agents avoid hypoglycemia, weight gain, and simplify the management of 
      T2DM. Dipeptidyl peptidase-4 (CD26, DPP4) inhibitors are the most widely used 
      incretin-based therapy for the treatment of T2DM globally. DPP4 inhibitors are 
      modestly effective in reducing HbA1c (glycated hemoglobin) ( approximately 0.5%) and while 
      these agents were synthesized with the understanding of the role that DPP4 plays 
      in prolonging the half-life of incretins such as glucagon-like peptide-1 and 
      gastric inhibitory peptide, it is now recognized that incretins are only one of 
      many targets of DPP4. The widespread expression of DPP4 on blood vessels, 
      myocardium, and myeloid cells and the nonenzymatic function of CD26 as a 
      signaling and binding protein, across a wide range of species, suggest a 
      teleological role in cardiovascular regulation and inflammation. Indeed, DPP4 is 
      upregulated in proinflammatory states including obesity, T2DM, and 
      atherosclerosis. Consistent with this maladaptive role, the effects of DPP4 
      inhibition seem to exert a protective role in cardiovascular disease at least in 
      preclinical animal models. Although 2 large clinical trials suggest a neutral 
      effect on cardiovascular end points, current limitations of performing trials in 
      T2DM over a limited time horizon on top of maximal medical therapy must be 
      acknowledged before rendering judgment on the cardiovascular efficacy of these 
      agents. This review will critically review the science of DPP4 and the effects of 
      DPP4 inhibitors on the cardiovascular system.
CI  - (c) 2015 American Heart Association, Inc.
FAU - Zhong, Jixin
AU  - Zhong J
AD  - From the Divisions of Cardiovascular Medicine and Endocrinology, University of 
      Maryland, Baltimore.
FAU - Maiseyeu, Andrei
AU  - Maiseyeu A
AD  - From the Divisions of Cardiovascular Medicine and Endocrinology, University of 
      Maryland, Baltimore.
FAU - Davis, Stephen N
AU  - Davis SN
AD  - From the Divisions of Cardiovascular Medicine and Endocrinology, University of 
      Maryland, Baltimore.
FAU - Rajagopalan, Sanjay
AU  - Rajagopalan S
AD  - From the Divisions of Cardiovascular Medicine and Endocrinology, University of 
      Maryland, Baltimore. srajagopalan@medicine.umaryland.edu.
LA  - eng
GR  - R01 ES017290/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - EC 3.4.14.5 (DPP4 protein, human)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Animals
MH  - Cardiovascular Diseases/diagnosis/*drug therapy/enzymology
MH  - Clinical Trials as Topic
MH  - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/enzymology
MH  - Dipeptidyl Peptidase 4/*metabolism
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Inflammation/diagnosis/*drug therapy/enzymology
MH  - Signal Transduction/drug effects
MH  - Treatment Outcome
PMC - PMC4394189
MID - NIHMS671686
OTO - NOTNLM
OT  - DPP4 protein, mouse
OT  - cardiovascular diseases
OT  - diabetes mellitus
OT  - glucagon-like peptide-1
OT  - incretins
EDAT- 2015/04/11 06:00
MHDA- 2015/06/13 06:00
PMCR- 2016/04/10
CRDT- 2015/04/11 06:00
PHST- 2015/04/11 06:00 [entrez]
PHST- 2015/04/11 06:00 [pubmed]
PHST- 2015/06/13 06:00 [medline]
PHST- 2016/04/10 00:00 [pmc-release]
AID - CIRCRESAHA.116.305665 [pii]
AID - 10.1161/CIRCRESAHA.116.305665 [doi]
PST - ppublish
SO  - Circ Res. 2015 Apr 10;116(8):1491-504. doi: 10.1161/CIRCRESAHA.116.305665.