Effect of Liraglutide on the Metabolic Profile in Patients with Type 2 Diabetes and Cardiovascular Disease

INTERVENTION: Trade Name: Victoza Product Name: Liraglutid Pharmaceutical Form: Injection Pharmaceutical form of the placebo: Solution for injection in pre‐filled pen Route of administration of the placebo: Subcutaneous use CONDITION: Diabetes Type 2 with existing cardiovascular disease Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: Effect of Liraglutide treatment for 3 months vs. placebo on metabolic profile of patients with type 2 diabetes and existing cardiovascular disease. Primary end point(s): Effect of Liraglutide 1.8 mg/d in comparison to placebo after 3 month on the metabolic profile using the discovery HD4 platform, which consists of 4 different methods: 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. Secondary Objective: Effect of Liraglutide treatment for 3 months vs. placebo on left ventricular systolic and diastolic function by echocardiography, energy expenditure and respiratory exchange ratio, the incidence of supraventricular and ventricular arrhythmias (24h holter ECG), systemic low grade inflammation as assessed by cytokine profile and circulating leukocyte populations and microbiome composition in patients with type 2 diabetes and existing cardiovascular disease. Timepoint(s) of evaluation of this end point: after 3 month SECONDARY OUTCOME: Secondary end point(s): Effect of Liraglutide in comparison to placebo after 3 months on:; ‐ 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; ‐ 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; ‐ change in left ventricular systolic function by ejection fraction (EF) by echocardiography; ‐ blood pressure; ‐ body weight; ‐ NT‐proBNP; ‐ lipid profile; ‐ serum levels of glucose, HbA1c, glucagon, insulin, C‐Peptide, ß‐Hydroxybutyrate; ‐ Heart rate variability (24 h ECG); ‐ Resting energy expenditure (measured by indirect calorimetry [CardioCoach CO2]); ‐ Respiratory Exchange Ratio (measured by indirect calorimetry [CardioCoach CO2]); ‐ Microbiome analysis by 16S metagenomics sequencing; ‐ Albumin excretion by 24 h urine collection; ‐ changes in inflammosome analyses assessed by cytokine array; ‐ changes in lipidomics analyses, parameters included in the metabolomic profile; ‐ changes in circulation inflammatory cell composition (flow cytometry analyses, FACS); ‐ serum and urine samples in addition to blood mononuclear cell pellets are stored for further analyses Timepoint(s) of evaluation of this end point: after 3 month INCLUSION CRITERIA: 1. Type 2 diabetes 2. Serum levels of HbA1c = 7,0% 3. Age = 18 years 4. Patients with existing cardiovascular disease: coronary heart disease, cerebrovascular disease, peripheral vascular disease or chronic kidney disease of stage III or greater or chronic heart failure of NYHA II or III 5. Written informed consent prior to study participation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25