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.
References42
Newest
Feb 1, 2021·Jacc-cardiovascular Imaging12.74
#1Alexander J.M. Brown (Dund.: University of Dundee)H-Index: 2
#1Alexander J. Brown (Dund.: University of Dundee)H-Index: 23
Last. Chim C. Lang (Dund.: University of Dundee)H-Index: 68
view all 8 authors...
Subclinical left ventricular (LV) dysfunction is highly prevalent in people with type 2 diabetes mellitus (T2DM) and is independently associated with poor cardiovascular outcome ([1][1]). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce hospitalizations for heart failure
2 CitationsSource
Dec 8, 2020·Journal of the American College of Cardiology20.59
#1Massar Omar (University of Southern Denmark)H-Index: 4
#2Jesper Jensen (UCPH: University of Copenhagen)H-Index: 13
Last. Jacob E. Møller (University of Southern Denmark)H-Index: 59
view all 13 authors...
Abstract Background Inhibition of the sodium-glucose cotransporter-2 (SGLT2i) improves outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but the mechanism by which they improve outcomes remains unclear. Objectives This study aimed to investigate the effects of sodium-glucose cotransporter-2 inhibitor empagliflozin on central hemodynamics in patients with HF and HFrEF. Methods This investigator-initiated, double-blinded, placebo-controlled, randomized trial enrol...
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Sep 25, 2020·Cardiovascular Diabetology7.33
#1Wataru Shimizu (Nippon Medical School)H-Index: 86
#2Embody trial investigators (Nippon Medical School)
Last. Embody trial investigatorsH-Index: 1
view all 19 authors...
Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium–glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. This prospective, multicenter, randomized, double-blind, placebo-co...
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Nov 19, 2019·Circulation23.60
#1Subodh VermaH-Index: 95
#1Subodh VermaH-Index: 26
Last. Empa-Heart CardioLink InvestigatorsH-Index: 1
view all 19 authors...
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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Oct 25, 2019·Scientific Reports4.00
#1Jung-Chi Hsu (NTU: National Taiwan University)H-Index: 2
#2Chih-Yuan Wang (NTU: National Taiwan University)H-Index: 22
Last. Wei-Shiung Yang (NTU: National Taiwan University)H-Index: 53
view all 5 authors...
Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that empagliflozin might have beneficial effects on cardiac function, structure, adiposity, and myocardial diffuse fibrosis. This prospective study enrolled 35 patients (48.6% men, age 63.5 ± 9.7 years) with type 2 diabetes mellitus (T2DM) from June 1, 2017, to November 31, 2018. The patients received an SGLT2 i...
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Oct 1, 2019·Esc Heart Failure3.90
#1Nick S.R. Lan (Fiona Stanley Hospital)H-Index: 5
#2P. Gerry Fegan (Fiona Stanley Hospital)H-Index: 5
Last. Girish Dwivedi (UWA: University of Western Australia)H-Index: 15
view all 4 authors...
Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti‐hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo‐controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associ...
23 CitationsSource
Sep 19, 2019·The New England Journal of Medicine74.70
#1John J.V. McMurray (Glas.: University of Glasgow)H-Index: 197
#1Harry Peled (St. Jude Medical Center)H-Index: 3
Last. AM LangkildeH-Index: 3
view all 38 authors...
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...
1,085 CitationsSource
Aug 1, 2019·Internal Medicine Journal1.68
#1Neale CohenH-Index: 20
#2Sarah J. GutmanH-Index: 7
Last. Andrew J. Taylor (Baker IDI Heart and Diabetes Institute)H-Index: 51
view all 4 authors...
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 ...
13 CitationsSource
Apr 30, 2019·Circulation23.60
#1Roni Nielsen (Aarhus University Hospital)H-Index: 16
#2Niels Møller (AU: Aarhus University)H-Index: 81
Last. Henrik Wiggers (AU: Aarhus University)H-Index: 20
view all 15 authors...
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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Mar 18, 2019·Diabetes Care16.02
#1Aino Latva-Rasku (UTU: University of Turku)H-Index: 4
#2Miikka-Juhani Honka (UTU: University of Turku)H-Index: 11
Last. Pirjo Nuutila (UTU: University of Turku)H-Index: 87
view all 13 authors...
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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May 26, 2021·Diabetes Therapy3.18
#1Gian Pio Sorice (UCSC: Catholic University of the Sacred Heart)H-Index: 17
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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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