Cooperation of Insulin and GLP-1 on Myocardial Glucose Uptake

Cooperation of Insulin and GLP-1 on Myocardial Glucose Uptake

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).

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).

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).