Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the effects of dapagliflozin on insulin sensitivity
Interventions
DRUGDapagliflozin
Tablets, Oral, 5 mg, once daily, 12 weeks
DRUGPlacebo
Tablets, Oral, 0 mg, Once daily, 12 weeks
Sponsors
Astra Zeneca, Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with type 2 diabetes and inadequate glycemic control, defined as A1C ≥ 7.0 and ≤ 10.0% at the enrollment visit * Subjects should have been receiving either metformin therapy OR metformin therapy AND one insulin secretagogue for at least 12 weeks prior to enrollment * C-peptide ≥ 1.0 ng/ml (0.34 nmol/l) * BMI ≤ 45.0 kg/m2
Exclusion criteria
* Urine albumin to creatinine ratio (UACR) \> 1,800 mg/g (203.4 mg/mmol/Cr) * Aspartate Aminotransferase (AST) \> 3X Upper limit of normal (ULN) * Alanine aminotransferase (ALT) \> 3X ULN * Serum Total Bilirubin \> 2 mg/dL (34.2 μmol/l) * Serum Creatinine (Scr) ≥ 1.50 mg/dL (133 μmol/l) for men; SCr ≥ 1.40 mg/dL (124 μmol/l) for women * Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 12 | Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 12 | Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period. |
Countries
United States
Participant flow
Recruitment details
Of 116 participants enrolled, 50 completed a qualification period. Of these 50 participants, 44 were randomized and received treatment. Of these 44 participants, 42 completed double-blind treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Background Anti-Diabetes Medication Placebo tablets, oral, once daily, 12 weeks | 21 |
| Dapagliflozin 5 mg + Background Anti-Diabetes Medication Dapagliflozin tablets, oral, once daily, 12 weeks | 23 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | No longer met criteria | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo + Background Anti-Diabetes Medication | Dapagliflozin 5 mg + Background Anti-Diabetes Medication | Total |
|---|---|---|---|
| Age, Continuous | 53.3 Years STANDARD_DEVIATION 8.02 | 56.2 Years STANDARD_DEVIATION 8.85 | 54.8 Years STANDARD_DEVIATION 8.49 |
| Age, Customized 65-70 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Customized Younger than 65 years | 18 Participants | 19 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 13 Participants | 28 Participants |
| Sex/Gender, Customized Female | 7 Participants | 8 Participants | 15 Participants |
| Sex/Gender, Customized Male | 14 Participants | 15 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 21 | 9 / 23 |
| serious Total, serious adverse events | 0 / 21 | 0 / 23 |
Outcome results
Primary
Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF])
Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.
Time frame: From Baseline to Week 12
Population: All randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Background Anti-Diabetes Medication | Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF]) | -9.99 % Change of Baseline Insulin Sensitivity | Standard Error 4.0392 |
| Dapagliflozin 5 mg + Background Anti-Diabetes Medication | Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF]) | 7.98 % Change of Baseline Insulin Sensitivity | Standard Error 4.4849 |
p-value: 0.005995% CI: [5.75, 36.1]ANOVA
Secondary
Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF])
Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.
Time frame: From Baseline to Week 12
Population: All randomized participants who received study medication and had nonmissing values at baseline and Week 12 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Background Anti-Diabetes Medication | Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF]) | -12.73 mU/L*min | Standard Error 10.7107 |
| Dapagliflozin 5 mg + Background Anti-Diabetes Medication | Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF]) | 15.39 mU/L*min | Standard Error 9.593 |
p-value: 0.059895% CI: [-1.22, 57.48]ANOVA