Type 2 Diabetes
Conditions
Keywords
T2DM, Metformin, A1c
Brief summary
The purpose of this study is to compare reduction in A1C for subjects taking Saxagliptin and Metformin XR vs. uptitrated Metformin XR.
Interventions
DRUGSaxagliptin
5mg oral tablet once daily
DRUGMetformin XR
500mg oral tablet once daily
Sponsors
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
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetics taking metformin IR or XR greater than or equal to 850mg and less than or equal to 1500mg only for at least 8 weeks prior to screening * A1c: 7.5-11% (at screening) * BMI less than or equal to 45 kg/m2
Exclusion criteria
* Significant cardiovascular history * Active liver disease, renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c Level From Baseline to Week 18 (LOCF) | Baseline to week 18 | Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Baseline to week 18 | Adjusted mean change from baseline in 2-hour PPG (following MMTT) achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). PPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value. |
| Change in FPG From Baseline to Week 18 (LOCF) | Baseline to week 18 | Adjusted mean change from baseline in FPG achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). FPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value. |
| Percent of Subjects Reaching Goal (HbA1c <7%) at Week 18 (LOCF) - Percent of Subjects (1) | Week 18 (LOCF) | Percent of subjects achieving therapeutic response (HbA1c \<7.0%) at Week 18 (LOCF) (Randomized analysis set) |
Countries
Colombia, Costa Rica, Mexico, Peru, United States
Participant flow
Pre-assignment details
Of the 393 subjects who entered the lead-in period, 111 subjects did not enter the randomized, double-blind treatment period. Thus, a total of 282 subjects were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin + Metformin Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL) | 138 |
| Metformin (DB) + Metformin (OL) Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL) | 144 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 7 |
| Overall Study | Did not attend the termination visit | 0 | 1 |
| Overall Study | Hyperglycemia | 1 | 5 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | No longer met study criteria | 1 | 5 |
| Overall Study | Severe non-compliance to protocol | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Saxagliptin + Metformin | Metformin (DB) + Metformin (OL) | Total |
|---|---|---|---|
| Age Continuous | 55.22 years STANDARD_DEVIATION 9.41 | 55.46 years STANDARD_DEVIATION 9.86 | 55.34 years STANDARD_DEVIATION 9.64 |
| Sex: Female, Male Female | 81 Participants | 71 Participants | 152 Participants |
| Sex: Female, Male Male | 57 Participants | 73 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 138 | 16 / 144 |
| serious Total, serious adverse events | 0 / 138 | 3 / 144 |
Outcome results
Primary
Change in HbA1c Level From Baseline to Week 18 (LOCF)
Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.
Time frame: Baseline to week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin + Metformin | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Baseline | 8.41 Percent | Standard Error 0.076 |
| Saxagliptin + Metformin | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Week 18 | 7.53 Percent | Standard Error 0.093 |
| Saxagliptin + Metformin | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -0.88 Percent | Standard Error 0.077 |
| Metformin (DB) + Metformin (OL) | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Baseline | 8.28 Percent | Standard Error 0.077 |
| Metformin (DB) + Metformin (OL) | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Week 18 | 7.93 Percent | Standard Error 0.111 |
| Metformin (DB) + Metformin (OL) | Change in HbA1c Level From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -0.35 Percent | Standard Error 0.076 |
95% CI: [-0.73, -0.31]
Secondary
Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF)
Adjusted mean change from baseline in 2-hour PPG (following MMTT) achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). PPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.
Time frame: Baseline to week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin + Metformin | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Baseline | 227.36 mg/dL | Standard Error 6.022 |
| Saxagliptin + Metformin | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Week 18 | 195.11 mg/dL | Standard Error 5.876 |
| Saxagliptin + Metformin | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -31.52 mg/dL | Standard Error 4.996 |
| Metformin (DB) + Metformin (OL) | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Baseline | 223.68 mg/dL | Standard Error 5.295 |
| Metformin (DB) + Metformin (OL) | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Week 18 | 216.24 mg/dL | Standard Error 6.23 |
| Metformin (DB) + Metformin (OL) | Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -8.20 mg/dL | Standard Error 5.081 |
95% CI: [-37.36, -9.28]
Secondary
Change in FPG From Baseline to Week 18 (LOCF)
Adjusted mean change from baseline in FPG achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). FPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.
Time frame: Baseline to week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saxagliptin + Metformin | Change in FPG From Baseline to Week 18 (LOCF) | Baseline | 162.54 mg/dL | Standard Error 4.146 |
| Saxagliptin + Metformin | Change in FPG From Baseline to Week 18 (LOCF) | Week 18 | 142.70 mg/dL | Standard Error 3.633 |
| Saxagliptin + Metformin | Change in FPG From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -20.03 mg/dL | Standard Error 3.146 |
| Metformin (DB) + Metformin (OL) | Change in FPG From Baseline to Week 18 (LOCF) | Baseline | 163.35 mg/dL | Standard Error 3.91 |
| Metformin (DB) + Metformin (OL) | Change in FPG From Baseline to Week 18 (LOCF) | Week 18 | 156.32 mg/dL | Standard Error 3.948 |
| Metformin (DB) + Metformin (OL) | Change in FPG From Baseline to Week 18 (LOCF) | Adjusted Change from Baseline to Week 18 | -6.85 mg/dL | Standard Error 3.09 |
95% CI: [-21.86, -4.5]
Secondary
Percent of Subjects Reaching Goal (HbA1c <7%) at Week 18 (LOCF) - Percent of Subjects (1)
Percent of subjects achieving therapeutic response (HbA1c \<7.0%) at Week 18 (LOCF) (Randomized analysis set)
Time frame: Week 18 (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin + Metformin | Percent of Subjects Reaching Goal (HbA1c <7%) at Week 18 (LOCF) - Percent of Subjects (1) | 37.2 Percentage of Participants |
| Metformin (DB) + Metformin (OL) | Percent of Subjects Reaching Goal (HbA1c <7%) at Week 18 (LOCF) - Percent of Subjects (1) | 26.1 Percentage of Participants |
p-value: 0.045995% CI: [0.2, 22]ANCOVA