Effects of Exenatide in Type 2 Diabetic Patients With Congestive Heart Failure

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Exenatide Compared to Insulin Glargine on Cardiac Function and Metabolism in Type 2 Diabetic Patients With Congestive Heart Failure: a Randomized Comparator-controlled Trial

Conditions
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Type 2 Diabetes Mellitus, Congestive Heart Failure

Intervention / Treatment
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* Drug: exenatide
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Exenatide<br> | Drug: exenatide<br>* Exenatide 5 mcg BID for 4 weeks, subsequently increased to 10 mcg BID for the remainder of the study (total of 26 weeks).<br>* Other names: exenatide-Byetta;|
| Active Comparator: 2. Insulin glargine<br> | Drug: Insulin glargine<br>* Insulin glargine will be initiated at 10 IU QD, titrated according to fasting blood glucose concentrations based on general protocol-defined guidance.<br>* Other names: insulin glargine-Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Magnetic Resonance (CMR) will be used to assess global cardiac function (LV ejection fraction). |  | week -2 and week 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exenatide, Type 2 diabetes mellitus, Congestive heart failure, Incretin hormones, GLP-1 agonist, Cardiac metabolism, Insulin resistance, Cardiac MRI