Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients-a description of the DAPACARD study.


Journal

Upsala journal of medical sciences
ISSN: 2000-1967
Titre abrégé: Ups J Med Sci
Pays: Sweden
ID NLM: 0332203

Informations de publication

Date de publication:
Jan 2019
Historique:
pubmed: 9 1 2019
medline: 13 9 2019
entrez: 9 1 2019
Statut: ppublish

Résumé

Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels. DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET). The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.

Sections du résumé

BACKGROUND BACKGROUND
Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels.
METHODS METHODS
DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET).
CONCLUSION CONCLUSIONS
The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.

Identifiants

pubmed: 30618324
doi: 10.1080/03009734.2018.1515281
pmc: PMC6450503
doi:

Substances chimiques

Benzhydryl Compounds 0
Biomarkers 0
Glucosides 0
SLC5A2 protein, human 0
Sodium-Glucose Transporter 2 0
dapagliflozin 1ULL0QJ8UC
Metformin 9100L32L2N

Types de publication

Clinical Trial, Phase IV Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

59-64

Références

Circulation. 2006 Nov 14;114(20):2130-7
pubmed: 17088453
N Engl J Med. 2007 Mar 15;356(11):1140-51
pubmed: 17360992
J Nucl Cardiol. 2007 May-Jun;14(3):354-65
pubmed: 17556170
Am J Cardiol. 2009 Jun 15;103(12):1721-6
pubmed: 19539082
J Clin Invest. 2014 Feb;124(2):499-508
pubmed: 24463454
J Magn Reson Imaging. 2015 Apr;41(4):1129-37
pubmed: 24700404
Heart. 2014 Nov;100(21):1673-80
pubmed: 24860005
Dev Cell. 2015 Mar 23;32(6):678-92
pubmed: 25752962
N Engl J Med. 2015 Nov 26;373(22):2117-28
pubmed: 26378978
Eur Heart J. 2016 Dec 07;37(46):3461-3469
pubmed: 26392437
J Magn Reson Imaging. 2016 Jul;44(1):178-85
pubmed: 26731196
Am J Physiol Endocrinol Metab. 2016 Mar 15;310(6):E452-60
pubmed: 26732686
Circ Cardiovasc Imaging. 2016 Mar;9(3):e003643
pubmed: 26962125
J Nucl Cardiol. 2016 Aug;23(4):670-9
pubmed: 27094041
N Engl J Med. 2016 Jul 28;375(4):311-22
pubmed: 27295427
Cell Metab. 2017 Jul 5;26(1):27-38
pubmed: 28506519
N Engl J Med. 2017 Aug 17;377(7):644-657
pubmed: 28605608
Circulation. 2017 Oct 24;136(17):1643-1658
pubmed: 29061576
Diabetes Care. 2018 Feb;41(2):356-363
pubmed: 29203583
Am J Nephrol. 2017 Dec 13;46(6):462-472
pubmed: 29253846
Diabetes Obes Metab. 2018 May;20(5):1102-1110
pubmed: 29322605
Eur J Endocrinol. 2018 Apr;178(4):R113-R125
pubmed: 29371333
N Engl J Med. 1998 Jul 23;339(4):229-34
pubmed: 9673301
Lancet. 1998 Sep 12;352(9131):854-65
pubmed: 9742977

Auteurs

Axel Åkerblom (A)

a Uppsala Clinical Research Center and Department of Medical Sciences , Uppsala University , Uppsala , Sweden.

Jonas Oldgren (J)

a Uppsala Clinical Research Center and Department of Medical Sciences , Uppsala University , Uppsala , Sweden.

Aino Latva-Rasku (A)

b Turku PET Centre , University of Turku , Turku , Finland.
c Department of endocrinology, Turku University Hospital , Turku , Finland.

Lars Johansson (L)

d Antaros Medical AB, Gothenburg , Sweden.

Vera Lisovskaja (V)

e AstraZeneca , Gothenburg , Sweden.

Cecilia Karlsson (C)

e AstraZeneca , Gothenburg , Sweden.

Jan Oscarsson (J)

e AstraZeneca , Gothenburg , Sweden.

Pirjo Nuutila (P)

b Turku PET Centre , University of Turku , Turku , Finland.
c Department of endocrinology, Turku University Hospital , Turku , Finland.

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Classifications MeSH