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.

Humans Incretins / therapeutic use Liraglutide / therapeutic use Plasminogen Activator Inhibitor 1 Prediabetic State / complications Fibrinolysis Insulin Resistance Diet, Reducing Obesity / complications Hypoglycemic Agents / therapeutic use Sitagliptin Phosphate / therapeutic use Weight Loss Inflammation / drug therapy Glucagon-Like Peptide-1 Receptor / agonists
DPP4 inhibitor GLP-1 receptor agonist cardiovascular disease dietary intervention incretin physiology randomized trial

Journal

Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645

Informations de publication

Date de publication:
02 2023
Historique:
revised: 10 10 2022
received: 29 07 2022
accepted: 24 10 2022
pmc-release: 01 02 2024
pubmed: 29 10 2022
medline: 5 1 2023
entrez: 28 10 2022
Statut: ppublish

Résumé

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. 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). 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). 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.

Identifiants

DOI: 10.1111/dom.14903 PMID: 36306151 PMC: PMC10306232
pubmed: 36306151
doi: 10.1111/dom.14903
pmc: PMC10306232
mid: NIHMS1845791
doi:

Substances chimiques

Incretins 0
Liraglutide 839I73S42A
Plasminogen Activator Inhibitor 1 0
Hypoglycemic Agents 0
Sitagliptin Phosphate TS63EW8X6F
Glucagon-Like Peptide-1 Receptor 0

Types de publication

Randomized Controlled Trial Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

570-580

Subventions

Organisme : NIDDK NIH HHS
ID : T32 DK007061
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI155299
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146654
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020593
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125426
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI095227
Pays : United States

Informations de copyright

© 2022 John Wiley & Sons Ltd.

Références

JACC Basic Transl Sci. 2022 Jul 25;7(7):713-715
pubmed: 35958685
Am J Epidemiol. 2008 May 15;167(10):1226-34
pubmed: 18385206
Arterioscler Thromb. 1993 Feb;13(2):162-9
pubmed: 8427853
Diabetes Obes Metab. 2013 Aug;15(8):770-3
pubmed: 23451821
Diabetes Res Clin Pract. 2014 Dec;106(3):567-75
pubmed: 25458329
Lancet Diabetes Endocrinol. 2021 Oct;9(10):653-662
pubmed: 34425083
Ther Adv Cardiovasc Dis. 2010 Oct;4(5):315-24
pubmed: 20660535
Circ Res. 2004 Jul 23;95(2):217-23
pubmed: 15178637
Cardiovasc Diabetol. 2018 Jan 8;17(1):8
pubmed: 29310645
Lancet. 2010 Jun 12;375(9731):2073-81
pubmed: 20483451
J Endocr Soc. 2019 Jul 01;3(10):1784-1798
pubmed: 31528826
Mol Metab. 2021 Apr;46:101102
pubmed: 33068776
Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H2-12
pubmed: 20952670
JAMA. 2018 Apr 17;319(15):1580-1591
pubmed: 29677303
J Hepatol. 2016 Feb;64(2):399-408
pubmed: 26394161
Diabetologia. 1991 Jul;34(7):457-62
pubmed: 1916049
J Clin Invest. 1991 Oct;88(4):1121-7
pubmed: 1843454
Eur J Clin Invest. 2016 Jun;46(6):564-71
pubmed: 27090943
Circulation. 2019 Apr 23;139(17):2022-2031
pubmed: 30786725
Int Immunopharmacol. 2021 Dec;101(Pt B):107598
pubmed: 34233864
Arch Intern Med. 2007 Dec 10;167(22):2490-6
pubmed: 18071172
J Diabetes Res. 2018 Dec 04;2018:1232583
pubmed: 30622967
Diab Vasc Dis Res. 2013 Jan;10(1):72-7
pubmed: 22732108
J Atheroscler Thromb. 2015;22(6):610-7
pubmed: 25737193
Circulation. 2001 Mar 27;103(12):1618-23
pubmed: 11273987
Clin Sci (Lond). 2020 Sep 18;134(17):2369-2379
pubmed: 32880388
Eur Heart J. 2022 May 14;43(19):1799-1808
pubmed: 35567558
Atherosclerosis. 2015 Mar;239(1):21-30
pubmed: 25568949
Br J Haematol. 2004 Aug;126(3):298-306
pubmed: 15257701
PLoS One. 2015 Aug 18;10(8):e0135854
pubmed: 26284918
Arterioscler Thromb Vasc Biol. 2021 Jun;41(6):2038-2048
pubmed: 33827260
Thromb Haemost. 2017 Jun 2;117(6):1115-1128
pubmed: 28405672
J Am Heart Assoc. 2014 Jan 03;3(1):e000609
pubmed: 24390146
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5252-6
pubmed: 2052604
Diabet Med. 2008 Sep;25(9):1129-31
pubmed: 19183322
Can J Cardiol. 2009 Jun;25 Suppl A:15A-20A
pubmed: 19521569
Circulation. 1998 Nov 24;98(21):2241-7
pubmed: 9826309
Int J Obes (Lond). 2012 Jun;36(6):843-54
pubmed: 21844879
Diabet Med. 2012 Sep;29(9):1115-8
pubmed: 22288732
J Interferon Cytokine Res. 2019 Apr;39(4):224-232
pubmed: 30730243
J Coll Physicians Surg Pak. 2019 Mar;29(3):218-221
pubmed: 30823945
J Clin Endocrinol Metab. 2012 Jan;97(1):198-207
pubmed: 22013105
J Interferon Cytokine Res. 2009 Jun;29(6):313-26
pubmed: 19441883
N Engl J Med. 2016 Jul 28;375(4):311-22
pubmed: 27295427
Clin Sci (Lond). 2017 Mar 1;131(5):343-353
pubmed: 28049736
Metabolism. 1986 Mar;35(3):250-3
pubmed: 3081778
Lancet Diabetes Endocrinol. 2016 Nov;4(11):913-921
pubmed: 27595918
Arterioscler Thromb Vasc Biol. 2001 Mar;21(3):327-34
pubmed: 11231910

Auteurs

Mona Mashayekhi (M)

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee.
ORCID: 0000-0003-0331-2395

Joshua A Beckman (JA)

Department of Medicine, Division of Vascular Medicine, UTSouthwestern, Dallas, Texas.
ORCID: 0000-0001-8332-8439

Hui Nian (H)

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

Erica M Garner (EM)

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee.

Dustin Mayfield (D)

Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.

Jessica K Devin (JK)

UCHealth Endocrinology, Yampa Valley Medical Center, Steamboat Springs, Colorado.

John R Koethe (JR)

Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee.

Jonathan D Brown (JD)

Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Katherine N Cahill (KN)

Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Chang Yu (C)

Department of Population Health, NYU Grossman School of Medicine, New York, New York.

Heidi Silver (H)

Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
Department of Medicine, Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee.

Kevin Niswender (K)

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee.
Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.

James M Luther (JM)

Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.

Nancy J Brown (NJ)

Yale School of Medicine, New Haven, Connecticut.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comparative effects of weight loss and...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Incrétines › Comparative effects of weight loss and...
Recherchemedicale.com › Hormones gastrointestinales › Peptides glucagon-like › Glucagon-like peptide 1 › Liraglutide › Comparative effects of weight loss and...
Recherchemedicale.com › Facteurs biologiques › Facteurs de la coagulation sanguine › Inhibiteurs d'activateurs du plasminogène › Inhibiteur-1 d'activateur du plasminogène › Comparative effects of weight loss and...
Recherchemedicale.com › Maladies endocriniennes › Diabète › État prédiabétique › Comparative effects of weight loss and...
Recherchemedicale.com › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémostase › Coagulation sanguine › Fibrinolyse › Comparative effects of weight loss and...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Insulinorésistance › Comparative effects of weight loss and...
Recherchemedicale.com › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Régime amaigrissant › Comparative effects of weight loss and...
Recherchemedicale.com › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Comparative effects of weight loss and...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Comparative effects of weight loss and...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Pyrazines › Phosphate de sitagliptine › Comparative effects of weight loss and...
Recherchemedicale.com › Phénomènes physiologiques › Croissance et développement › Croissance › Mensurations corporelles › Poids › Modifications du poids corporel › Perte de poids › Comparative effects of weight loss and...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Comparative effects of weight loss and...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormone gastrointestinale › Récepteurs des peptides similaires au glucagon › Récepteur du peptide-1 similaire au glucagon › Comparative effects of weight loss and...