Congestive Heart Failure, Type 2 Diabetes Mellitus
Conditions
Keywords
Exenatide, Type 2 diabetes mellitus, Congestive heart failure, Incretin hormones, GLP-1 agonist, Cardiac metabolism, Insulin resistance, Cardiac MRI
Brief summary
The purpose of this study is to determine if exenatide will improve global cardiac function in patients with type 2 diabetes mellitus and congestive heart failure, by favorable effects on cardiac metabolism leading to improvement of cardiac efficiency.
Interventions
DRUGexenatide
Exenatide 5 mcg BID for 4 weeks, subsequently increased to 10 mcg BID for the remainder of the study (total of 26 weeks).
DRUGInsulin glargine
Insulin glargine will be initiated at 10 IU QD, titrated according to fasting blood glucose concentrations based on general protocol-defined guidance.
Sponsors
Amsterdam UMC, location VUmc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Type 2 diabetes mellitus * Male and postmenopausal female * Age 18 years an above * Metformin therapy (stable, maximum tolerable dose for 2 months) * HbA1c 6.5-10% * Confirmed congestive heart failure (NHYA functional class II-IV) * Ejection fraction \< 50% * Patients should receive a stable standard therapy for their cardiac condition for 3 months prior entering the study
Exclusion criteria
* Type 1 diabetes mellitus * Serious renal or liver impairment * (Receiving treatment for) malignant disease * Cardiovascular event \< 3 months prior to inclusion * Acute congestive heart failure * Any reason for not being able to sustain the imaging studies * Pacemaker/ICD * Contraindications for the use of exenatide/ insulin * Use of insulin, thiazolidinediones, incretin-based therapies within 4 months of screening * Chronic use of glucocorticoids, NSAIDs or centrally acting drugs (\> 2 weeks) within 2 weeks immediately prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cardiac Magnetic Resonance (CMR) will be used to assess global cardiac function (LV ejection fraction). | week -2 and week 11 |
Secondary
| Measure | Time frame |
|---|---|
| Cardiac oxygen consumption, cardiac efficiency and stress perfusion will be assessed by Positron Emission Tomography (PET) using 11C-acetate and H2-15O | week -2 and week 26 |
| Cardiac function, dimensions and scarring will be measured bij CMR | week -2 and week 26 |
| Myocardial diastolic function parameters will be obtained bij trans thoracal echocardiography. Comparisons will be made of strain and torsion measures obtained bij CMR and echocardiography. | week -2 and week 26 |
| Exercise capacity and performance will be assessed by a 6-minute walking test | week -1 and week 27 |
Countries
Netherlands
Outcome results
None listed