Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to compare the effects of saxagliptin with those of placebo as add-on therapy to insulin and insulin with metformin in improving glycemic control at 24 and 52 weeks.
Interventions
DRUGSaxagliptin, 5 mg + insulin
Saxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue)
DRUGPlacebo + insulin
Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus * Must have been taking a stable dose of basal or premixed insulin for 8 weeks or longer prior to screening * If taking metformin, must have been taking the same daily dose for 8 weeks or longer prior to screening * Insulin type should be intermediate- or long-acting (basal) or premixed (premixed formulation may include short- or rapid-acting insulin as 1 component). * Inadequate glycemic control (A1C of 7.5% to 11.0%, inclusive) * Body mass index of 45 kg/m² or lower * Fasting C-peptide level of 0.8 ng/mL or higher
Exclusion criteria
* Symptoms of poorly controlled diabetes, including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the last 3 months prior to screening or other signs and symptoms * History of diabetic ketoacidosis or hyperosmolar nonketotic coma * Women of childbearing potential unable or unwilling to use acceptable birth control * Women who are pregnant or breastfeeding * Active liver disease * Anemia * Chronic or repeated intermittent corticosteroid treatment (participants receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be enrolled) * Use of short- or rapid-acting insulin * Significant cardiovascular history defined as: myocardial infarction, coronary angioplasty or bypass graft, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident * Congestive heart failure * Unstable or rapidly progressing renal disease * History of alcohol or drug abuse within the previous year * History of hemoglobinopathies * Unstable major psychiatric disorders * Immunocompromised status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) | Baseline to Week 24 | Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) | Baseline to Week 24 | An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal |
| Change From Baseline in 120-minute PPG Values During an MTT | Baseline to Week 24 | An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal. |
| Change From Baseline in Fasting Plasma Glucose Values | Baseline to Week 24 | — |
| Percentage of Participants Achieving a Therapeutic Glycemic Response | Baseline to Week 24 | Therapeutic glycemic response is defined as an A1C\<7%. Significance was not interpreted with a p value. |
| Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) | Baseline to Week 24 | Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Baseline and during and up to 14 days after last dose of study drug (in Week 52) | Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment. Criteria 1: if prx=0 use \>=2, if prx=0.5 or 1 use \>=3, if prx=2 use 4. |
| Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results | Baseline to Week 52 | ECG abnormalities included those in nonspecific other categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions. |
| Percentage of Participants With Reported and Confirmed Hypoglycemia | Baseline to Week 52 | Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/ |
| Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline and Weeks 24 and 52 | Absolute lymphocyte count=value\*10\^3 c/uL |
| Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Baseline to Week 52, continuously | An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. |
| Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 | — |
| Mean Changes From Baseline in Heart Rate | Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 | — |
| Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline and Weeks 24 and 52 | Platelet count=value\*10\^9 c/L |
Countries
Canada, France, Hungary, India, Mexico, Poland, Russia, South Africa, United Kingdom, United States
Participant flow
Pre-assignment details
Of 455 participants randomized, 402 received treatment and completed the 24-week phase. Two participants were mistakenly identified as not completing the short-term (ST) treatment period, although they did. The discrepancy was identified after the ST phase database lock. In reality, 404 completed the ST phase.
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin, 5 mg + Insulin Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes | 304 |
| Placebo + Insulin Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes | 151 |
| Total | 455 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: Short-term (24-week) Phase | Adverse Event | 6 | 3 |
| Period 1: Short-term (24-week) Phase | Death | 1 | 0 |
| Period 1: Short-term (24-week) Phase | Lack of Efficacy | 3 | 2 |
| Period 1: Short-term (24-week) Phase | Lost to Follow-up | 3 | 5 |
| Period 1: Short-term (24-week) Phase | No longer meets study criteria | 5 | 0 |
| Period 1: Short-term (24-week) Phase | Other | 0 | 1 |
| Period 1: Short-term (24-week) Phase | Poor compliance or noncompliance | 5 | 1 |
| Period 1: Short-term (24-week) Phase | Withdrawal by Subject | 13 | 5 |
| Period 2: Long-term (52-week) Phase | Adverse Event | 4 | 0 |
| Period 2: Long-term (52-week) Phase | Lack of Efficacy | 1 | 0 |
| Period 2: Long-term (52-week) Phase | Lost to Follow-up | 1 | 1 |
| Period 2: Long-term (52-week) Phase | No longer meets study criteria | 5 | 4 |
| Period 2: Long-term (52-week) Phase | Other | 1 | 0 |
| Period 2: Long-term (52-week) Phase | Poor or noncompliance | 5 | 2 |
| Period 2: Long-term (52-week) Phase | Pregnancy | 1 | 0 |
| Period 2: Long-term (52-week) Phase | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Total | Saxagliptin, 5 mg + Insulin | Placebo + Insulin |
|---|---|---|---|
| Age, Customized 65 years to younger than 75 years | 95 participants | 65 participants | 30 participants |
| Age, Customized 75 years and older | 9 participants | 6 participants | 3 participants |
| Age, Customized Younger than 65 years | 351 participants | 233 participants | 118 participants |
| Age, Customized | 57.2 Years STANDARD_DEVIATION 9.37 | 57.2 Years STANDARD_DEVIATION 9.43 | 58 years FULL_RANGE 9.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 59 Participants | 40 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 13 Participants | 9 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 | 19 Participants | 14 Participants | 5 Participants |
| Race (NIH/OMB) White | 355 Participants | 237 Participants | 118 Participants |
| Sex: Female, Male Female | 267 Participants | 184 Participants | 83 Participants |
| Sex: Female, Male Male | 188 Participants | 120 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 151 | 96 / 304 |
| serious Total, serious adverse events | 13 / 151 | 25 / 304 |
Outcome results
Primary
Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])
Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use
Time frame: Baseline to Week 24
Population: Randomized participants who received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24- and 52-week periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) | -0.73 Percentage of change | Standard Error 0.054 |
| Placebo + Insulin | Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) | -0.32 Percentage of change | Standard Error 0.074 |
p-value: <0.000195% CI: [-0.59, -0.24]ANCOVA
Secondary
Change From Baseline in 120-minute PPG Values During an MTT
An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Change From Baseline in 120-minute PPG Values During an MTT | -27.2 mg/dL | Standard Error 4.35 |
| Placebo + Insulin | Change From Baseline in 120-minute PPG Values During an MTT | -4.2 mg/dL | Standard Error 6.08 |
p-value: 0.001695% CI: [-37.2, -8.7]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose Values
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Change From Baseline in Fasting Plasma Glucose Values | -10.1 mg/dL | Standard Error 2.87 |
| Placebo + Insulin | Change From Baseline in Fasting Plasma Glucose Values | -6.1 mg/dL | Standard Error 3.98 |
p-value: 0.395895% CI: [-13.32, 5.28]ANCOVA
Secondary
Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)
Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline.
Time frame: Baseline to Week 24
Population: Randomized participants who received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24-week period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) | 1.71 Units | Standard Error 0.704 |
| Placebo + Insulin | Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) | 5.01 Units | Standard Error 0.97 |
95% CI: [-5.6, -1.1]ANCOVA
Secondary
Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)
An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) | -4548.5 mg*min/dL | Standard Error 687.65 |
| Placebo + Insulin | Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) | -718.8 mg*min/dL | Standard Error 981.63 |
p-value: 0.001195% CI: [-6122.4, -1537.1]ANCOVA
Secondary
Percentage of Participants Achieving a Therapeutic Glycemic Response
Therapeutic glycemic response is defined as an A1C\<7%. Significance was not interpreted with a p value.
Time frame: Baseline to Week 24
Population: Randomized participants who received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24-week period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin, 5 mg + Insulin | Percentage of Participants Achieving a Therapeutic Glycemic Response | 17.3 Percentage of participants |
| Placebo + Insulin | Percentage of Participants Achieving a Therapeutic Glycemic Response | 6.7 Percentage of participants |
Other Pre-specified
Mean Changes From Baseline in Heart Rate
Time frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 2 (n=294, 147) | -0.5 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 4 (n=293, 144) | -0.5 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 6 (n=280, 141) | -0.5 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 8 (n=290, 142) | -0.0 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 12 (n=286, 144) | 0.3 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 16 (n=278, 139) | -1.0 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 20 (n=276, 137) | -0.5 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 24 (n=273, 134) | 0.0 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 28 (n=264, 132) | -1.0 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 36 (n=261, 129) | 0.0 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 44 (n=250, 125) | 0.2 Beats per minute |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Heart Rate | Week 52 (n=246, 125) | -0.3 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 44 (n=250, 125) | -0.7 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 2 (n=294, 147) | -0.7 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 20 (n=276, 137) | 0.4 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 4 (n=293, 144) | -1.0 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 36 (n=261, 129) | -0.0 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 6 (n=280, 141) | -0.9 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 24 (n=273, 134) | -1.0 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 8 (n=290, 142) | -0.7 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 52 (n=246, 125) | 0.2 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 12 (n=286, 144) | 0.2 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 28 (n=264, 132) | -0.6 Beats per minute |
| Placebo + Insulin | Mean Changes From Baseline in Heart Rate | Week 16 (n=278, 139) | -0.6 Beats per minute |
Other Pre-specified
Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings
Time frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 16) (n=278, 139) | -1.1 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 8) (n=290, 142) | -0.8 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 12) (n=286, 144) | -1.7 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 6) (n=280, 141) | 0.0 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 8) (n=290, 142) | -0.5 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 12) (n=286, 144) | -0.8 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 2) (n=294, 147) | -1.0 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 20) (n=276, 137) | -0.7 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 24) (n=273, 134) | -1.7 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 28) (n=264, 132) | -1.6 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 36) (n=261, 129) | -1.2 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 44) (n=250, 125) | -0.3 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 52) (n=246, 125) | -0.5 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 4) (n=293, 144) | -1.2 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 6) (n=280, 141) | -0.8 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 16) (n=278, 139) | -1.2 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 20) (n=276, 137) | -0.6 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 24) (n=273, 134) | -1.5 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 28) (n=264, 132) | -1.4 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 36) (n=261, 129) | -0.7 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 44) (n=250, 125) | -0.6 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 52) (n=246, 125) | 0.0 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 2) (n=294, 147) | 0.1 mm Hg |
| Saxagliptin, 5 mg + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 4) (n=293, 144) | 0.0 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 2) (n=294, 147) | 1.4 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 6) (n=280, 141) | 1.0 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 52) (n=246, 125) | 0.1 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 8) (n=290, 142) | 2.4 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 2) (n=294, 147) | 2.3 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 12) (n=286, 144) | 2.2 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 28) (n=264, 132) | 1.8 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 6) (n=280, 141) | 0.3 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 4) (n=293, 144) | 0.0 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 8) (n=290, 142) | 2.1 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 52) (n=246, 125) | 1.0 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 12) (n=286, 144) | 1.0 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 36) (n=261, 129) | 3.6 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 16) (n=278, 139) | 1.3 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 16) (n=278, 139) | 1.1 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 20) (n=276, 137) | 1.1 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 4) (n=293, 144) | 1.8 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 24) (n=273, 134) | 0.5 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 20) (n=276, 137) | 1.3 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 28) (n=264, 132) | 0.2 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 44) (n=250, 125) | 2.6 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 36) (n=261, 129) | 0.2 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Systolic blood pressure (Week 24) (n=273, 134) | -0.1 mm Hg |
| Placebo + Insulin | Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings | Diastolic blood pressure (Week 44) (n=250, 125) | 0.4 mm Hg |
Other Pre-specified
Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results
ECG abnormalities included those in nonspecific other categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions.
Time frame: Baseline to Week 52
Population: Participants who had normal ECG findings at baseline and who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin, 5 mg + Insulin | Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results | 15 Participants |
| Placebo + Insulin | Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results | 11 Participants |
Other Pre-specified
Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs
An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time frame: Baseline to Week 52, continuously
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 treatment-related AE | 56 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 9 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 treatment-related SAE | 3 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 AE | 202 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 SAE | 25 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Deaths | 2 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Discontinuations due to SAEs | 4 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Discontinuations due to SAEs | 0 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Deaths | 0 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 SAE | 13 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 treatment-related SAE | 0 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 AE | 108 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 3 Participants |
| Placebo + Insulin | Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs | At least 1 treatment-related AE | 34 Participants |
Other Pre-specified
Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period
Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment. Criteria 1: if prx=0 use \>=2, if prx=0.5 or 1 use \>=3, if prx=2 use 4.
Time frame: Baseline and during and up to 14 days after last dose of study drug (in Week 52)
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Creatinine >2.5 mg/dL (n=303; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Eosinophils >0.9*1000 c/uL (n=296; 150) | 9 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum fasting <50 mg/dL (n=0; 0) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >10*ULN (n=298; 148) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum fasting >500 mg/dL (n=0; 0) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Platelets <50*10^9 c/L (n=297; 145) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum unspecified <50 mg/dL (n=0; 0) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >20*ULN (n=298; 148) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum unspecified >500 mg/dL (n=0; 0) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Lymphocytes <=0.75*1000 c/uL (n=296; 150) | 3 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma fasting <50 mg/dL (n=301;150) | 5 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >3*ULN (n=300; 148) | 5 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma fasting >500 mg/dL (n=301;150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Leukocytes <2*1000 c/uL (n=300; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma unspecified <50 mg/dL (n=272; 133) | 5 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >5*ULN (n=300; 148) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma unspecified >500 mg/d (n=272; 133) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alkaline phosphatase >3*prx & >ULN (n=302; 150) | 2 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Sodium, serum <0.9*prx & <=130 mEq/L (n=302; 150) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >10*ULN (n=300; 148) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Sodium, serum >1.1*prx & >=150 mEq/L (n=302; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Hematocrit <0.75*prx (n=300; 150) | 2 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Potassium, serum <0.8 prx &<=3.2 mEq/L(n=300; 148) | 3 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >20*ULN (n=300; 148) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Potassium, serum >1.2*prx&>= 6.0 mEq/L(n=300; 148) | 8 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alkaline phosphatase >1.5 ULN (n=302; 150) | 10 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Chloride, serum <90 mEq/L (n=302; 150) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >2 mg/dL (n=301; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Chloride, serum >120 mEq/L (n=302; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Neutrophils <1*1000 c/uL (n=296; 150) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Albumin <0.9*LLN; if prx<LLN, 0.75*prx (n=302,150) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >1.5*ULN (n=301; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Creatine kinase >5*ULN (n=301, 148) | 6 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >3* ULN (n=298; 148) | 2 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Uric acid >1.5*ULN; if prx >ULN, >2 (n=0,0) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >2*ULN (n=301; 150) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Protein urine (see criteria 1) (n=297,146) | 8 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Platelets >1.5*ULN (n=297; 145) | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Blood urine (see criteria 1) (n=297; 146) | 14 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Blood urea nitrogen >2*prx & >ULN (n=302; 150) | 5 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Red blood cells urine (see criteria 1) (n=53; 31) | 8 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase>5* ULN (n=298; 148) | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | White blood cells urine (see criteria 1)(n=115;53) | 35 Participants |
| Saxagliptin, 5 mg + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Hemoglobin <8 g/dL (n=300; 150) | 2 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | White blood cells urine (see criteria 1)(n=115;53) | 10 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Hemoglobin <8 g/dL (n=300; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Hematocrit <0.75*prx (n=300; 150) | 2 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Platelets <50*10^9 c/L (n=297; 145) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Platelets >1.5*ULN (n=297; 145) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Leukocytes <2*1000 c/uL (n=300; 150) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Neutrophils <1*1000 c/uL (n=296; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Eosinophils >0.9*1000 c/uL (n=296; 150) | 7 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Lymphocytes <=0.75*1000 c/uL (n=296; 150) | 2 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alkaline phosphatase >3*prx & >ULN (n=302; 150) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alkaline phosphatase >1.5 ULN (n=302; 150) | 5 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >3* ULN (n=298; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase>5* ULN (n=298; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >10*ULN (n=298; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Aspartate aminotransferase >20*ULN (n=298; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >3*ULN (n=300; 148) | 3 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >5*ULN (n=300; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >10*ULN (n=300; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Alanine transaminase >20*ULN (n=300; 148) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >2 mg/dL (n=301; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >1.5*ULN (n=301; 150) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Bilirubin, total >2*ULN (n=301; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Blood urea nitrogen >2*prx & >ULN (n=302; 150) | 7 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Creatinine >2.5 mg/dL (n=303; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum fasting <50 mg/dL (n=0; 0) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum fasting >500 mg/dL (n=0; 0) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum unspecified <50 mg/dL (n=0; 0) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, serum unspecified >500 mg/dL (n=0; 0) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma fasting <50 mg/dL (n=301;150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma fasting >500 mg/dL (n=301;150) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma unspecified <50 mg/dL (n=272; 133) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Glucose, plasma unspecified >500 mg/d (n=272; 133) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Sodium, serum <0.9*prx & <=130 mEq/L (n=302; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Sodium, serum >1.1*prx & >=150 mEq/L (n=302; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Potassium, serum <0.8 prx &<=3.2 mEq/L(n=300; 148) | 1 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Potassium, serum >1.2*prx&>= 6.0 mEq/L(n=300; 148) | 8 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Chloride, serum <90 mEq/L (n=302; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Chloride, serum >120 mEq/L (n=302; 150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Albumin <0.9*LLN; if prx<LLN, 0.75*prx (n=302,150) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Creatine kinase >5*ULN (n=301, 148) | 2 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Uric acid >1.5*ULN; if prx >ULN, >2 (n=0,0) | 0 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Protein urine (see criteria 1) (n=297,146) | 3 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Blood urine (see criteria 1) (n=297; 146) | 2 Participants |
| Placebo + Insulin | Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period | Red blood cells urine (see criteria 1) (n=53; 31) | 3 Participants |
Other Pre-specified
Percentage of Participants With Reported and Confirmed Hypoglycemia
Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/
Time frame: Baseline to Week 52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Percentage of Participants With Reported and Confirmed Hypoglycemia | Reported | 19.4 Percentage of Participants |
| Saxagliptin, 5 mg + Insulin | Percentage of Participants With Reported and Confirmed Hypoglycemia | Confirmed | 7.6 Percentage of Participants |
| Placebo + Insulin | Percentage of Participants With Reported and Confirmed Hypoglycemia | Reported | 24.5 Percentage of Participants |
| Placebo + Insulin | Percentage of Participants With Reported and Confirmed Hypoglycemia | Confirmed | 6.6 Percentage of Participants |
Other Pre-specified
Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)
Absolute lymphocyte count=value\*10\^3 c/uL
Time frame: Baseline and Weeks 24 and 52
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 >0.75- <= 5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 <= 0.75 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 <= 0.75 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 >0.75- <= 5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 >5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 >5.00 | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 >5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 <= 0.75 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 <= 0.75 | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 >0.75- <= 5.00 | 295 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 >5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 >0.75- <= 5.00 | 293 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 <= 0.75 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 >0.75- <= 5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 >0.75- <= 5.00 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 >5.00 | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 >5.00 | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 >5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 >0.75- <= 5.00 | 2 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 >5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 >0.75- <= 5.00 | 2 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 24 >5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 >0.75- <= 5.00 | 148 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 24 >5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 >0.75- <= 5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 24 >5.00 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline <= 0.75; Week 52 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 >0.75- <= 5.00 | 147 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >0.75- <= 5.00; Week 52 >5.00 | 1 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 <= 0.75 | 0 Participants |
| Placebo + Insulin | Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) | Baseline >5.00; Week 52 >0.75- <= 5.00 | 0 Participants |
Other Pre-specified
Shift in Platelet Counts From Baseline to Selected Visits (LOCF)
Platelet count=value\*10\^9 c/L
Time frame: Baseline and Weeks 24 and 52
Population: All participants who received at least 1 dose of double-blind study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 >100 - <= 600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 <= 100 | 2 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 >100 - <= 600 | 295 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 <= 100 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 >100 - <= 600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 <= 100 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 >100 - <= 600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 <= 100 | 1 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 >100 - <= 600 | 296 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 <= 100 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 >100 - <= 600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 >600 | 0 Participants |
| Saxagliptin, 5 mg + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 >100 - <= 600 | 1 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 >100 - <= 600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 52 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 >100 - <= 600 | 144 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 52 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 <= 100 | 1 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 >100 - <= 600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >100 - <= 600; Week 24 >100 - <= 600 | 143 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 52 >600 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline <= 100; Week 24 <= 100 | 0 Participants |
| Placebo + Insulin | Shift in Platelet Counts From Baseline to Selected Visits (LOCF) | Baseline >600; Week 24 >100 - <= 600 | 0 Participants |