Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Dapagliflozin, Placebo, Insulin resistance, Insulin sensitivity
Brief summary
This is an 8-week, single centre, randomized, parallel-group, double-blind, placebo-controlled Phase IV study to evaluate the effect of dapagliflozin on tissue specific insulin sensitivity in patients with Type 2 diabetes mellitus
Interventions
DRUGPlacebo
Matching placebo to Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks
DRUGDapagliflozin
Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks
Sponsors
Antaros Medical
Bioventure Hub
43183 Mölndal
Sweden
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Provision of signed informed consent prior to any study specific procedures. 2. Female or male aged 35 to 70 years inclusive with suitable veins for cannulation or repeated venipuncture 3. Type 2 Diabetes mellitus defined as HbA1c of ≥ 6.5% and ≤ 10.5%. 4. Stable (≥ 3 months) T2D treatment with metformin and/or metformin+dipeptidyl peptidase-4 inhibitors (DPP-IV) 5. Body mass index (BMI) ≤ 40 kg/m2. 6. Female subjects must be of non-childbearing potential, meeting at least one of the following criteria: 1. Hysterectomized females 2. Postmenopausal women, defined as women who have not had a menstrual period within 1 year Main
Exclusion criteria
1. Any condition that is contraindicated with MRI such as, but not limited to, having a pacemaker or claustrophobia. 2. Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status. 3. Recent Cardiovascular Events in a patient: * Acute Coronary Syndrome (ACS) within 2 months prior to enrolment * Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment * Acute Stroke or Transient Ischemic Attack (TIA) within two months prior to enrolment * Less than two months post coronary artery revascularization 4. Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure. 5. Blood pressure at enrolment: Systolic BP ≥165 mm Hg and/or diastolic BP ≥100 mm Hg 6. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of the investigational product. 7. On insulin, GLP-1 or other oral antidiabetic drug treatment (metformin or both metformin and DPP-IV allowed) or using other medications known to affect glucose metabolism. 8. Any clinically significant abnormalities in physical examination, Electrocardiography (ECG) or clinical chemistry results as judged by the investigator. The following specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake | From baseline to Week 8 | Adjusted change from baseline in skeletal muscle insulin-stimulated gluocose uptake (umol/min/kg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake | Baseline to Week 8 | Change in adipose tissue insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET |
| Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8 | Baseline to Week 8 | Adjusted change in liver insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET |
Countries
Finland
Participant flow
Recruitment details
A total of 55 subjects were enrolled and 32 subjects were randomised and treated. One participant was withdrawn prior to study completion. Thirty-one participants completed the study and attended all visits.
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin 10 MG Dapagliflozin 10 MG added to stable metformin, dipeptidyl pepdidase-4 (DPP-IV) inhibitor, or sulphonylurea alone or in combination with either metformin or DPP-IV inhibitor antidiabetic medication. | 15 |
| Placebo Placebo added to stable metformin, dipeptidyl pepdidase-4 (DPP-IV) inhibitor, or sulphonylurea alone or in combination with either metformin or DPP-IV inhibitor antidiabetic medication. | 16 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Dapagliflozin 10 MG |
|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 7.4 | 61.0 years STANDARD_DEVIATION 7.9 | 62.1 years STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 31 Participants | 15 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 7 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake
Adjusted change from baseline in skeletal muscle insulin-stimulated gluocose uptake (umol/min/kg)
Time frame: From baseline to Week 8
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin 10 MG | Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake | 0.28 umol/min/kg | Standard Error 1.23 |
| Placebo | Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake | 0.28 umol/min/kg | Standard Error 1.13 |
p-value: 0.998495% CI: [-3.07, 3.07]ANCOVA
Secondary
Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake
Change in adipose tissue insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET
Time frame: Baseline to Week 8
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin 10 MG | Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake | 1.04 umol/min/kg | Standard Error 1.5 |
| Placebo | Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake | -0.64 umol/min/kg | Standard Error 1.36 |
p-value: 0.379495% CI: [-2.18, 5.54]ANCOVA
Secondary
Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8
Adjusted change in liver insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET
Time frame: Baseline to Week 8
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dapagliflozin 10 MG | Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8 | 0.27 umol/min/kg | Standard Error 1.74 |
| Placebo | Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8 | 1.59 umol/min/kg | Standard Error 1.52 |
p-value: 0.531795% CI: [-5.6, 2.96]ANCOVA