This is a randomised, placebo-controlled, double-blind, parallel-group, international, multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency and myocardial contractile work in T2D patients. Eligible subjects with T2D before randomisation and fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1 ratio to dapagliflozin 10 mg or placebo once daily and treated for six weeks. The study includes five visits.
The following will be assessed at Baseline and at the end of the treatment period; 1. MRI scanning in order to assess cardiac function and morphology. The MRI scanning will be made after fasting for at least 6 hours in the same time of day at all visits. The cardiac MRI examination will be performed in accordance with a pre-defined MRI protocol, with the total scan time at each visit estimated to 45 minutes. Images from all sites will be analyzed centrally at the core-lab using a dedicated software package and certified analysts. 2. CT-PET scanning will be made to assess myocardial function and metabolism, as well as fatty acid metabolism in brain, liver and kidney cortex. The CT-PET scanning will be made after a fast as well as abstinence from nicotine, alcohol and caffeine for at least 6 hours at the same time of day at all visits. * A cardiac 11C-Acetate PET/CT examination is performed (IV 400 MBq 11C-Acetate). * A cardiac 18F-FTHA PET/CT examination is performed (IV 150 MBq 18F-FTHA). The subject is further examined by PET/CT over the liver, kidney cortex and brain (in this order) for uptake of 18F-FTHA. Arterialized venous samples are acquired throughout to assess P-NEFA and 18F-FTHA metabolism by metabolite analysis
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
53
dapagliflozin 10mg
placebo to match dapagliflozin
Research Site
Turku, Finland
Research Site
Uppsala, Sweden
Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.
Patients underwent magnetic resonance imaging (MRI) examination to determine the GLSLV, which is expressed as a percentage. The least square mean (LSM) change from baseline estimates were generated from an analysis of covariance (ANCOVA) model with treatment and baseline value of the endpoint as covariates.
Time frame: Baseline (Day 1) and end of treatment (Day 42)
Adjusted Mean Change From Baseline in Myocardial Efficiency at End of Treatment.
A clinical radiologic assessment of acquired computed tomography and positron emission tomography (CTPET)-\[11C\]-acetate images was performed to determine myocardial efficiency. The myocardial efficiency calculation was based on an estimate of energy used for producing LV contractile work (mean arterial pressure (MAP) x stroke volume (SV) x heart rate (HR) / myocardial mass) compared to the total cardiac work (calculated based on the total myocardial oxygen consumption per myocardial mass) and is expressed as a percentage. The LSM change from baseline estimates, were generated from an ANCOVA model with treatment and baseline value of the endpoint as covariates.
Time frame: Baseline (Day 1) and end of treatment (Day 42)
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