Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo-controlled, exploratory study.

Published on Mar 12, 2021in Diabetes, Obesity and Metabolism5.9
· DOI :10.1111/DOM.14363
Jonas Oldgren51
Estimated H-index: 51
(Uppsala University),
Sanna M. Laurila1
Estimated H-index: 1
(TYKS: Turku University Hospital)
+ 13 AuthorsPirjo Nuutila87
Estimated H-index: 87
(TYKS: Turku University Hospital)
Sources
Abstract
Aims To explore early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and methods Patients with type 2 diabetes on metformin treatment were randomized to double-blind 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging (MRI); cardiac oxygen consumption, perfusion and efficiency with [11 C]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18 F]-FTHA PET, analyzed by ANCOVA as least square means with 95% confidence intervals. Results Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had mean age 64.4 years, BMI 30.2 kg/m2 , and HbA1c 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin vs placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work -0.095 (-0.145, -0.043) J/g/min, and LV oxygen consumption were significantly reduced -0.30 (-0.49, -0.12) J/g/min by dapagliflozin, but changes were not statistically significant vs changes in placebo group. Change in left atrial maximal volume with dapagliflozin vs placebo was -3.19 (-6.32, -0.07) mL/m2 , p = 0.056. Peak global radial strain decreased with dapagliflozin vs placebo, -3.92 (-7.57, -0.28) %, p = 0.035; peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin vs placebo, 0.024 (0.004, 0.044) μmol/g/min, p = 0.018, while cardiac uptake was unchanged. Conclusions This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency, and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks treatment with dapagliflozin. Clinical trial registration NCT03387683. This article is protected by copyright. All rights reserved.
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Background: SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to d...
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Abstract Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...
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The effects of empagliflozin on cardiac structure and function are not known AIMS: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with Type 2 (T2D) diabetes using cardiac magnetic resonance (MR) imaging. 20 patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patient with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent cardiac MR ...
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Background: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased c...
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OBJECTIVE The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA 1c 6.5–10.5% (48–91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were...
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#1Gian Pio Sorice (UCSC: Catholic University of the Sacred Heart)H-Index: 17
#2Francesca Cinti (UCSC: Catholic University of the Sacred Heart)H-Index: 6
Last. Andrea Giaccari (UCSC: Catholic University of the Sacred Heart)H-Index: 32
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INTRODUCTION Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to have beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) in primary prevention and in those with a high CV risk profile. However, the mechanism(s) responsible for these CV benefits remain elusive and unexplained. The aim of the DAPAHEART study will be to demonstrate that treatment with SGLT-2 inhibitors is associated with greater myocardial insulin sensitivity in pati...
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