PMID- 36306151
OWN - NLM
STAT- MEDLINE
DCOM- 20230104
LR  - 20240202
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 25
IP  - 2
DP  - 2023 Feb
TI  - Comparative effects of weight loss and incretin-based therapies on vascular 
      endothelial function, fibrinolysis and inflammation in individuals with obesity 
      and prediabetes: A randomized controlled trial.
PG  - 570-580
LID - 10.1111/dom.14903 [doi]
AB  - AIM: To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) 
      agonists have beneficial effects on vascular endothelial function, fibrinolysis 
      and inflammation through weight loss-independent mechanisms. MATERIALS AND 
      METHODS: Individuals with obesity and prediabetes were randomized to 14 weeks of 
      the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 
      inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and 
      placebo-controlled. Measurements were made at baseline, after 2 weeks prior to 
      significant weight loss and after 14 weeks. The primary outcomes were measures of 
      endothelial function: flow-mediated vasodilation (FMD), plasminogen activator 
      inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR). RESULTS: 
      Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, 
      sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and 
      PAI-1, while sitagliptin did not. There was no significant effect of any 
      treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup 
      analyses in individuals with baseline FMD below the median, indicative of greater 
      endothelial dysfunction, showed an improvement in FMD by all three treatments. 
      GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not 
      change FMD or PAI-1. There was no effect of treatment on UACR. Finally, 
      liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte 
      chemoattractant protein-1 (MCP-1). CONCLUSION: Liraglutide and diet reduce 
      weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not 
      change FMD in obese individuals with prediabetes with normal endothelial 
      function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic 
      chemokine MCP-1, indicating that this beneficial effect is independent of weight 
      loss.
CI  - (c) 2022 John Wiley & Sons Ltd.
FAU - Mashayekhi, Mona
AU  - Mashayekhi M
AUID- ORCID: 0000-0003-0331-2395
AD  - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, 
      Vanderbilt University Medical Center, Nashville, Tennessee.
FAU - Beckman, Joshua A
AU  - Beckman JA
AUID- ORCID: 0000-0001-8332-8439
AD  - Department of Medicine, Division of Vascular Medicine, UTSouthwestern, Dallas, 
      Texas.
FAU - Nian, Hui
AU  - Nian H
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, 
      Tennessee.
FAU - Garner, Erica M
AU  - Garner EM
AD  - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, 
      Vanderbilt University Medical Center, Nashville, Tennessee.
FAU - Mayfield, Dustin
AU  - Mayfield D
AD  - Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University 
      Medical Center, Nashville, Tennessee.
FAU - Devin, Jessica K
AU  - Devin JK
AD  - UCHealth Endocrinology, Yampa Valley Medical Center, Steamboat Springs, Colorado.
FAU - Koethe, John R
AU  - Koethe JR
AD  - Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
AD  - Department of Medicine, Division of Infectious Diseases, Vanderbilt University 
      Medical Center, Nashville, Tennessee.
FAU - Brown, Jonathan D
AU  - Brown JD
AD  - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt 
      University Medical Center, Nashville, Tennessee.
FAU - Cahill, Katherine N
AU  - Cahill KN
AD  - Department of Medicine, Division of Allergy, Pulmonary and Critical Care 
      Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
FAU - Yu, Chang
AU  - Yu C
AD  - Department of Population Health, NYU Grossman School of Medicine, New York, New 
      York.
FAU - Silver, Heidi
AU  - Silver H
AD  - Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
AD  - Department of Medicine, Division of Gastroenterology, Vanderbilt University 
      Medical Center, Nashville, Tennessee.
FAU - Niswender, Kevin
AU  - Niswender K
AD  - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, 
      Vanderbilt University Medical Center, Nashville, Tennessee.
AD  - Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
FAU - Luther, James M
AU  - Luther JM
AD  - Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University 
      Medical Center, Nashville, Tennessee.
FAU - Brown, Nancy J
AU  - Brown NJ
AD  - Yale School of Medicine, New Haven, Connecticut.
LA  - eng
GR  - T32 DK007061/DK/NIDDK NIH HHS/United States
GR  - U01 AI155299/AI/NIAID NIH HHS/United States
GR  - R01 HL146654/HL/NHLBI NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 HL125426/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
GR  - UL1 TR002243/TR/NCATS NIH HHS/United States
GR  - U19 AI095227/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221110
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Incretins)
RN  - 839I73S42A (Liraglutide)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Hypoglycemic Agents)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
SB  - IM
MH  - Humans
MH  - Incretins/therapeutic use
MH  - Liraglutide/therapeutic use
MH  - Plasminogen Activator Inhibitor 1
MH  - *Prediabetic State/complications/drug therapy
MH  - Fibrinolysis
MH  - *Insulin Resistance
MH  - Diet, Reducing
MH  - Obesity/complications/drug therapy
MH  - Hypoglycemic Agents/therapeutic use
MH  - Sitagliptin Phosphate/therapeutic use
MH  - Weight Loss
MH  - Inflammation/drug therapy
MH  - Glucagon-Like Peptide-1 Receptor/agonists
PMC - PMC10306232
MID - NIHMS1845791
OTO - NOTNLM
OT  - DPP4 inhibitor
OT  - GLP-1 receptor agonist
OT  - cardiovascular disease
OT  - dietary intervention
OT  - incretin physiology
OT  - randomized trial
COIS- None unless noted below: J.A.B.: Dr. Beckman is a consultant for JanOne, serves 
      on a DSMB for Janssen and Novartis, and has ownership in EMX and Janacare. J.R.K: 
      Dr. Koethe has served as a consultant to Gilead Sciences, Merck, ViiV Healthcare, 
      Theratechnologies and Janssen. He has also received research support from Gilead 
      Sciences and Merck. J.M.L: Dr. Luther has served on the advisory board for 
      Mineralys. N.J.B.: Dr. Brown serves on the scientific advisory board for Alnylam 
      Pharmaceuticals. She serves as a consultant for Pharvaris Gmbh and eBioStar Tech. 
      Dr. Brown owns equity in Abbvie and J and J Pharmaceuticals.
EDAT- 2022/10/29 06:00
MHDA- 2023/01/05 06:00
PMCR- 2024/02/01
CRDT- 2022/10/28 11:42
PHST- 2022/10/10 00:00 [revised]
PHST- 2022/07/29 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/10/29 06:00 [pubmed]
PHST- 2023/01/05 06:00 [medline]
PHST- 2022/10/28 11:42 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - 10.1111/dom.14903 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2023 Feb;25(2):570-580. doi: 10.1111/dom.14903. Epub 2022 
      Nov 10.