Type 2 Diabetes
Conditions
Keywords
Diabetes, Myocardial metabolism
Brief summary
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
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).
Interventions
DRUGliraglutide
1.8mg subcutaneous qd for 3 months
DRUGinsulin detemir
5units subcutaneous bid titrated to fasting glucose of \<130mg/dL for 3 months
DRUGliraglutide plus insulin detemir
liraglutide 1.8mg subq qd plus insulin detemir 5units bid titrated to fasting blood glucose \<130mg/dL for 3 months.
Sponsors
Indiana University
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Glucose Uptake | 3 months | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir |
| Myocardial Fatty Acid Oxidation Rate | 3 months | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir |
| Myocardial Fatty Acid Esterification Rate | 3 months | PET measurements of myocardial glucose uptake will be done after 3 months of exposure to liraglutide, insulin detemir, or liraglutide plus insulin detemir |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iiraglutide 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.
liraglutide: 1.8mg subcutaneous qd for 3 months | 9 |
| Insulin Detemir 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.
insulin detemir: 5units subcutaneous bid titrated to fasting glucose of \<130mg/dL for 3 months | 9 |
| Liraglutide Plus Insulin Detemir 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.
liraglutide plus insulin detemir: liraglutide 1.8mg subq qd plus insulin detemir 5units bid titrated to fasting blood glucose \<130mg/dL for 3 months. | 9 |
| Total | 27 |
Baseline characteristics
| Characteristic | Iiraglutide | Insulin Detemir | Liraglutide Plus Insulin Detemir | Total |
|---|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 5.3 | 52.1 years STANDARD_DEVIATION 8.6 | 49.2 years STANDARD_DEVIATION 9 | 51.7 years STANDARD_DEVIATION 7.6 |
| HbA1c, % | 7.59 % STANDARD_DEVIATION 0.96 | 7.00 % STANDARD_DEVIATION 0.79 | 8.13 % STANDARD_DEVIATION 0.99 | 7.57 % STANDARD_DEVIATION 0.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 2 Participants | 14 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 27 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 1 / 10 | 0 / 11 |
| other Total, other adverse events | 0 / 9 | 0 / 10 | 2 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 | 0 / 11 |
Outcome results
Primary
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
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iiraglutide | Myocardial Fatty Acid Esterification Rate | 0.00274 umol/g/min |
| Insulin Detemir | Myocardial Fatty Acid Esterification Rate | 0.00358 umol/g/min |
| Liraglutide Plus Insulin Detemir | Myocardial Fatty Acid Esterification Rate | 0.00146 umol/g/min |
p-value: 0.8Kruskal-Wallis
Primary
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
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iiraglutide | Myocardial Fatty Acid Oxidation Rate | 0.1019 umol/g/min |
| Insulin Detemir | Myocardial Fatty Acid Oxidation Rate | 0.1234 umol/g/min |
| Liraglutide Plus Insulin Detemir | Myocardial Fatty Acid Oxidation Rate | 0.0992 umol/g/min |
p-value: 0.065Kruskal-Wallis
Primary
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
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iiraglutide | Myocardial Glucose Uptake | 0.055 umol/g/min |
| Insulin Detemir | Myocardial Glucose Uptake | 0.0399 umol/g/min |
| Liraglutide Plus Insulin Detemir | Myocardial Glucose Uptake | 0.0373 umol/g/min |
p-value: 0.65Kruskal-Wallis