In an unbiased metabolomics approach with subsequent pathway analyses, the current study seeks to examine the effect of Liraglutide treatment on the metabolic signature in treated patients as well as the effect of Liraglutide on various echocardiographic parameters of cardiac function and rhythm profile, thus paving the way for future research to explain the effects of Liraglutide on cardiovascular mortality and overall mortality in treated patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Increasing dose of Liraglutide: 0.6 mg/d for the first week, 1.2 mg/d for the second week aiming for a maximum of 1.8 mg/d beginning with the third week (or highest tolerated dose).Subcutaneous injection once daily via pre-filled pen
Matching Placebo once daily, subcutaneous injection via pre-filled pen.
Department of Internal Medicine I, University Hospital
Aachen, Germany
Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months
Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months measured by a platform including 2 separate reverse phase (RP)/UPLC-MS/MS with positive ion mode electrospray ionization (ESI), (RP)/UPLC-MS/MS with negative ESI, and (HILIC)/UPLC-MS/MS with negative ESI.
Time frame: 3 month
change in left ventricular diastolic function
change in left ventricular diastolic function between baseline and after 12 weeks as determined by 2D and 3D parameter global Strain Rate E by echocardiography
Time frame: 3 month
change in left ventricular diastolic function
change in left ventricular diastolic function between baseline and after 12 weeks as determined by standardized parameter E/é and left atrial (LA) volume by echocardiography
Time frame: 3 month
change in left ventricular systolic function
change in left ventricular systolic function by ejection fraction (EF) by echocardiography
Time frame: 3 month
Changes in systolic and diastolic blood pressure (mmHg)
Changes in systolic and diastolic blood pressure (mmHg) between Liraglutide treatment group and placebo group after 1 and 3 months.
Time frame: 3 month
body weight
Time frame: 3 month
Changes in NT-proBNP serum levels (pg/ml)
Changes in NT-proBNP serum levels (pg/ml) between Liraglutide treatment group versus placebo group after 1 and 3 months.
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Time frame: 3 month
Differences of the serum lipid profile between Liraglutide treatment group and placebo group
Differences of the serum lipid profile including serum levels of triglycerides (mg/dl), total cholesterol (mg/dl), low-density lipoprotein cholesterol (mg/dl) and high-density lipoprotein cholesterol (mg/dl)between Liraglutide treatment group and placebo group after 1 and 3 months
Time frame: 3 month
changes of serum levels of glucose, HbA1c, glucagon, insulin, C-Peptide, β-Hydroxybutyrate between Liraglutide treatment group and placebo group
Changes in serum levels of glucose (mg/dl), HbA1c (%), glucagon (pg/ml), insulin (ng/ml), C-Peptide (ng/ml), β-Hydroxybutyrate (mmol/l) between Liraglutide treatment group and placebo group after 1 and 3 months
Time frame: 3 month
Heart rate variability
Differences in heart rate variability measured by 24 hour ECG between Liraglutide treatment group and placebo group after 3 month including the following parameters: mean heart rate (bpm), maximum/minimum heart rate (bpm) and long-term variation of RR intervals (defined as standard deviation over 24 hours of per-minute means of RR intervals).
Time frame: 3 month
Resting energy expenditure
Resting energy expenditure measured by indirect calorimetry \[CardioCoach CO2\]
Time frame: 3 month
Respiratory Exchange Ratio
Respiratory Exchange Ratio measured by indirect calorimetry \[CardioCoach CO2\]
Time frame: 3 month
Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group
Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group after 1 and 3 month including the following parameters: alpha diversity (reported as Shannon diversity index) and differences in bacterial composition at different taxonomic levels including genus, family and class of bacteria (reported as relative abundance).
Time frame: 3 month
Albumin excretion
Albumin excretion by 24 h urine collection
Time frame: 3 month
changes in inflammasome analyses
Differences in serum levels of inflammatory cytokines including C-reactive protein (mg/ml), Interleukin 6 (pg/ml), Interleukin 1 beta (pg/ml) and tumor necrosis factor alpha (pg/ml) between Liraglutide treatment group and placebo group after 1 and 3 month
Time frame: 3 month
Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group
Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group after 1 and 3 month including the following parameters: Numbers of T-cells including T-cell subsets and monocytes including monocyte subsets. Numbers will be reported as percentage of parent, i.e. total pool of CD45+ immune cells).
Time frame: 3 month