Cooperation of Insulin and GLP-1 on Myocardial Glucose Uptake

Study Overview
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Brief Summary
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27 Type 2 diabetic subjects (HbA1c 7.5 - 9.5%) currently treated with diet and exercise alone or with oral antidiabetic agents will be randomly assigned to one of three treatment groups: insulin detemir, liraglutide, or liraglutide plus detemir (9 subjects per group), on a background of metformin 2000 mg per day. After 3 months' treatment, PET measurements of myocardial fuel selection will take place, under fasting conditions in the morning following that day's treatment injection(s).

Detailed Description
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The investigators will test the hypothesis that effects of liraglutide plus insulin detemir on myocardial fuel selection will be greater than the effects of either agent alone. 27 Type 2 diabetic subjects (HbA1c 7.5 - 9.5%) currently treated with diet and exercise alone or with oral antidiabetic agents will be randomly assigned to one of three treatment groups: insulin detemir, liraglutide, or liraglutide plus detemir (9 subjects per group). All subjects will undergo an initial standardization of background treatment to metformin 2000 mg per day, followed by randomized assignment to 3 months' treatment with liraglutide 1.8 mg/day (once daily each morning, tapering up according to label instructions) and/or detemir (administered twice daily, initially at 10 units per day then titrated to achieve fasting morning glucose readings below 130 mg/dL). PET measurements of myocardial fuel selection will take place at the end of this treatment period, under fasting conditions in the morning following that day's treatment injection(s).

Official Title
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Cooperation of Insulin and GLP-1 on Myocardial Glucose Uptake

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: liraglutide
* Drug: insulin detemir
* Drug: liraglutide plus insulin detemir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetic 18-50 years BMI > 25kg/m2 HbA1c 7.0-10.0% Treated with up to 2 oral agents Exclusion Criteria: Chronic illness or infection (other than diabetes mellitus) Known coronary artery disease, structural heart disease or abnormal ECG on screen. Treatment with >2 antihypertensive agents or blood pressure >140/95 on two occasions during screening History of claustrophobia, musculoskeletal or other factors which would result in an inability to comfortably remain within the PET scanner gantry for the duration of the imaging protocol. Occupational, investigational or other known radiation exposure which together with the planned radiologic studies, will result in greater than 500 mrem total exposure in a 12 month period. Current pregnancy Treatment with GLP-1 agonist or DPP4 inhibitor within the past 6 months Known intolerance to GLP-1 agonist Personal history of pancreatitis, personal or family history of medullary thyroid carcinoma, or other contraindications to liraglutide treatment. Recognized microvascular complications (neuropathy, nephropathy, retinopathy).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iiraglutide<br>Type 2 diabetic subjects will be assigned to 3 months of treatment with 1.8mg liraglutide administered once daily in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment. | Drug: liraglutide<br>* 1.8mg subcutaneous qd for 3 months<br>* Other names: Victoza;|
| Experimental: insulin detemir<br>Type 2 diabetic subjects will be assigned to 3 months of treatment with insulin detemir administered twice daily in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment. | Drug: insulin detemir<br>* 5units subcutaneous bid titrated to fasting glucose of <130mg/dL for 3 months<br>* Other names: Levemir;|
| Experimental: Liraglutide plus insulin detemir<br>Type 2 diabetic subjects will be assigned to 3 months of treatment with a combination of liraglutide and insulin detemir in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment. | Drug: liraglutide plus insulin detemir<br>* liraglutide 1.8mg subq qd plus insulin detemir 5units bid titrated to fasting blood glucose <130mg/dL for 3 months.<br>* Other names: Vyctoza plus Levemir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Glucose Uptake | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir | 3 months | 
| Myocardial Fatty Acid Oxidation Rate | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir | 3 months | 
| Myocardial Fatty Acid Esterification Rate | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Myocardial metabolism