Type 2 Diabetes
Conditions
Keywords
epicardial fat, diabetes, dapagliflozin
Brief summary
The purpose of this research study is to learn about the effect of Dapagliflozin (Farxiga) on the fat of the heart.
Interventions
DRUGDapagliflozin
5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily.
DRUGMetformin
500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL
DRUGPlacebo
Placebo pill taken once daily to mimic Dapagliflozin
Sponsors
AstraZeneca
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes, as defined by ADA criteria * HbA1c \< 8% measured at least 1 week prior to the study * BMI ≥27 kg/m2 * Pre-treatment with Metformin as monotherapy * Age \> 18 and \< 65 years old * Normal and stable hemodynamic status
Exclusion criteria
* Known contra-indications to Farxiga, in accordance with risks and safety information included in the latest updated Prescribing Information * Type 1 diabetes, as defined by American Diabetes Association (ADA) criteria * Insulin dependent or treated type 2 diabetes * Current use of other SGLT2 inhibitors, Glucagon Like Peptide -1 (GLP- 1) analogs or Dipeptidyl Peptidase 4 (DPP4) inhibitors * Glomerular Filtration Rate (GFR) \< 60 mL/min/1.73 m2 * Signs or symptoms of hypovolemia * Patients with poor glycemic control (HbA1c ≥ 8%) will be excluded to maximize long-term patient retention without need * History of diabetes ketoacidosis * Patients with active bladder cancer or with a prior history of bladder cancer * Acute or chronic infective, including genital mycotic infections * Clinical signs or symptoms of New York Heart Association (NYHA) class III-IV heart failure * Clinical or laboratory evidences of chronic active liver diseases * Acute or chronic infective diseases * Cancer or chemotherapy * Current use of systemic corticosteroids or in the 3 months prior this study * Known or suspected allergy to Dapagliflozin, excipients, or related products * Pregnant, breast-feeding or the intention of becoming pregnant * Females of childbearing potential who are not using adequate contraceptive methods
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epicardial Fat Thickness | At Baseline, 12 weeks, 24 weeks | Epicardial fat thickness will be measured in millimeters by treating physician using echocardiography at Baseline, 12 weeks, 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Mass (LVM) | At Baseline, Week 12 and Week 24 | LVM will be measured in g/m\^2 by treating physician using echocardiography at baseline, Week 12 and Week 24 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dapagliflozin and Metformin Group Participants in this group will receive Dapagliflozin in addition to Metformin for 6 months.
Dapagliflozin: 5 mg taken orally once daily. After 2 weeks, if there are no safety issues as per treating physician discretion, the dose can be titrated up to 10 mg orally taken once daily.
Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL | 50 |
| Metformin and Placebo Group Participants in this group will receive Metformin and Placebo for 6 months.
Metformin: 500 mg taken orally twice daily to a maximum of 1000 mg twice daily to achieve a fasting glucose between 80-140 md/dL
Placebo: Placebo pill taken once daily to mimic Dapagliflozin | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Dapagliflozin and Metformin Group | Metformin and Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 9 | 51 years STANDARD_DEVIATION 11 | 51.5 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 22 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 28 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 29 Participants | 30 Participants | 59 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 8 / 50 | 2 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
Primary
Epicardial Fat Thickness
Epicardial fat thickness will be measured in millimeters by treating physician using echocardiography at Baseline, 12 weeks, 24 weeks
Time frame: At Baseline, 12 weeks, 24 weeks
Population: Data is reported only for the participants that completed the study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin and Metformin Group | Epicardial Fat Thickness | Baseline | 8.6 mm | Standard Deviation 2.2 |
| Dapagliflozin and Metformin Group | Epicardial Fat Thickness | 12 Weeks | 7.2 mm | Standard Deviation 2.3 |
| Dapagliflozin and Metformin Group | Epicardial Fat Thickness | 24 Weeks | 6.7 mm | Standard Deviation 2.1 |
| Metformin and Placebo Group | Epicardial Fat Thickness | Baseline | 8.0 mm | Standard Deviation 2.5 |
| Metformin and Placebo Group | Epicardial Fat Thickness | 12 Weeks | 7.4 mm | Standard Deviation 2.5 |
| Metformin and Placebo Group | Epicardial Fat Thickness | 24 Weeks | 7.5 mm | Standard Deviation 2.4 |
Secondary
Left Ventricular Mass (LVM)
LVM will be measured in g/m\^2 by treating physician using echocardiography at baseline, Week 12 and Week 24
Time frame: At Baseline, Week 12 and Week 24
Population: Due to time and technical limitations, LVM data were not collected for all participants that completed the study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dapagliflozin and Metformin Group | Left Ventricular Mass (LVM) | Baseline | 129 g/m^2 | Standard Deviation 13 |
| Dapagliflozin and Metformin Group | Left Ventricular Mass (LVM) | Week 12 | 127 g/m^2 | Standard Deviation 18 |
| Dapagliflozin and Metformin Group | Left Ventricular Mass (LVM) | Week 24 | 122 g/m^2 | Standard Deviation 19 |
| Metformin and Placebo Group | Left Ventricular Mass (LVM) | Baseline | 130 g/m^2 | Standard Deviation 19 |
| Metformin and Placebo Group | Left Ventricular Mass (LVM) | Week 12 | 128 g/m^2 | Standard Deviation 20 |
| Metformin and Placebo Group | Left Ventricular Mass (LVM) | Week 24 | 122 g/m^2 | Standard Deviation 20 |