Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes, exenatide once weekly, Byetta, sitagliptin, Januvia, thiazolidinedione, Amylin, Lilly, Pioglitazone
Brief summary
This study will compare the benefits of exenatide once weekly treatment to those achieved by the approved antidiabetic therapies sitagliptin and pioglitazone in subjects whose type 2 diabetes is managed with metformin therapy alone. The safety and tolerability of the three treatment regimens will also be compared.
Interventions
subcutaneous injection, 2.0mg, once a week
DRUGsitagliptin
oral tablet, 100mg, once a day
DRUGpioglitazone
oral tablet, 45mg, once a day
DRUGplacebo tablet
oral tablet, once a day
subcutaneous injection, once a week
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has been diagnosed with type 2 diabetes mellitus * Has a hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at study start * Has a body mass index (BMI)of 25 kg/m2 to 45 kg/m2, inclusive, at study start * Has been on a stable treatment regimen of metformin for a minimum of 2 months prior to study start * Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start: 1. Hormone replacement therapy (female subjects) 2. Oral contraceptives (female subjects) 3. Antihypertensive agents 4. Lipid-lowering agents 5. Thyroid replacement therapy 6. Antidepressant agents 7. Drugs known to affect body weight, including prescription medications (e.g. orlistat \[XENICAL®\], sibutramine \[MERIDIA®\], topiramate \[TOPAMAX®\]) and over-the-counter antiobesity agents
Exclusion criteria
* Has been previously exposed to exenatide once weekly * Has donated blood within 60 days of study start or is planning to donate blood during the study * Currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications: 1. Exenatide (BYETTA®) or any Dipeptidyl peptidase-4 DPP-4)inhibitor, sulfonylurea (SU), thiazolidinedione (TZD), or glucagon-like peptide (GLP)-1 analog within 3 months prior to study start 2. Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start 3. Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start 4. Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption 5. Drugs interacting with the CYP2C8 enzyme system, including gemfibrozil (LOPID®) and rifampin * Has received any investigational drug within 1 month (or five half-lives of investigational drug, whichever is greater) of study start * Has previously experienced a clinically significant adverse event (e.g., significant edema) related to TZD or DPP-4 inhibitor use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 26 | Day 1, Week 26 | Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 | Week 26 | Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 26. |
| Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 | Week 26 | Percentages of subjects achieving HbA1c target values of \<=6.0% at Week 26. |
| Change in Body Weight From Baseline to Week 26 | Day 1, Week 26 | Change in body weight from baseline (Day 1) to Week 26. |
| Change in Fasting Plasma Glucose From Baseline to Week 26 | Day 1, Week 26 | Change in fasting plasma glucose from baseline (Day 1) to Week 26. |
| Change in Systolic Blood Pressure From Baseline to Week 26 | Day 1, Week 26 | Change in systolic blood pressure from baseline (Day 1) to Week 26. |
| Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 | Week 26 | Percentages of subjects achieving HbA1c target values of \<7% at Week 26. |
| Change in Fasting Total Cholesterol From Baseline to Week 26 | Day 1, Week 26 | Change in fasting total cholesterol from baseline (Day 1) to Week 26. |
| Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 | Day 1, Week 26 | Change in fasting HDL from baseline (Day 1) to Week 26. |
| Ratio of Fasting Triglycerides at Week 26 to Baseline | Day 1, Week 26 | Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline. |
| Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Day 1 to Week 26 | Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration \< 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration \< 54 mg/dL prior to treatment and not classified as major hypoglycemia. |
| Change in Diastolic Blood Pressure From Baseline to Week 26 | Day 1, Week 26 | Change in diastolic blood pressure from baseline (Day 1) to Week 26. |
Countries
India, Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Once Weekly Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning | 160 |
| Sitagliptin Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly | 166 |
| Pioglitazone Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly | 165 |
| Total | 491 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative | 2 | 0 | 0 |
| Overall Study | Adverse Event | 11 | 5 | 7 |
| Overall Study | Investigator Decision | 1 | 3 | 1 |
| Overall Study | Loss of Glucose Control | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 8 | 9 | 13 |
| Overall Study | Protocol Violation | 2 | 4 | 1 |
| Overall Study | Withdrawal of Consent | 18 | 6 | 18 |
Baseline characteristics
| Characteristic | Exenatide Once Weekly | Total | Pioglitazone | Sitagliptin |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 59 Participants | 22 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 140 Participants | 432 Participants | 143 Participants | 149 Participants |
| Age, Continuous | 52.4 years STANDARD_DEVIATION 10.41 | 52.5 years STANDARD_DEVIATION 10.28 | 53.0 years STANDARD_DEVIATION 9.92 | 52.2 years STANDARD_DEVIATION 10.54 |
| Glycosylated hemoglobin (HbA1c) | 8.6 percentage of total hemoglobin STANDARD_DEVIATION 1.2 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.15 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.08 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.17 |
| Sex: Female, Male Female | 71 Participants | 237 Participants | 86 Participants | 80 Participants |
| Sex: Female, Male Male | 89 Participants | 254 Participants | 79 Participants | 86 Participants |
| Weight | 89.1 kg STANDARD_DEVIATION 19.55 | 88.0 kg STANDARD_DEVIATION 20.08 | 87.9 kg STANDARD_DEVIATION 20.49 | 87.0 kg STANDARD_DEVIATION 20.25 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 81 / 160 | 59 / 166 | 61 / 165 |
| serious Total, serious adverse events | 4 / 160 | 5 / 166 | 10 / 165 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26
Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\].
Time frame: Day 1, Week 26
Population: The ITT Population included randomized subjects who received at least one injection of study medication. Missing data up to Week 26 were imputed using the last observation carried forward (LOCF) approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in HbA1c From Baseline to Week 26 | -1.55 percentage of total hemoglobin | Standard Error 0.1 |
| Sitagliptin | Change in HbA1c From Baseline to Week 26 | -0.92 percentage of total hemoglobin | Standard Error 0.099 |
| Pioglitazone | Change in HbA1c From Baseline to Week 26 | -1.23 percentage of total hemoglobin | Standard Error 0.099 |
Comparison: Null hypothesis: no difference across treatments. Alternative hypothesis: a difference exists between exenatide once weekly and at least one comparator group (sitagliptin or pioglitazone). Power: Assuming 10% dropout, delta=0.5%, and common SD=1.2%, 450 subjects would provide \>90% power to detect a treatment difference (alpha=0.05, two-sided) in the change in HbA1c between exenatide once weekly and sitagliptin or pioglitazone, with Hochberg's multiplicity adjustment method.p-value: <0.000195% CI: [0.37, 0.89]ANOVA
Comparison: Null hypothesis: no difference across treatments. Alternative hypothesis: a difference exists between exenatide once weekly and at least one comparator group (sitagliptin or pioglitazone). Power: Assuming 10% dropout, delta=0.5%, and common SD=1.2%, 450 subjects would provide \>90% power to detect a treatment difference (alpha=0.05, two-sided) in the change in HbA1c between exenatide once weekly and sitagliptin or pioglitazone, with Hochberg's multiplicity adjustment method.p-value: 0.016595% CI: [0.06, 0.57]ANOVA
Secondary
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration \< 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration \< 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Time frame: Day 1 to Week 26
Population: ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Major Hypoglycemia | 0.00 rate per subject-year | Standard Error 0 |
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Minor Hypoglycemia | 0.03 rate per subject-year | Standard Error 0.021 |
| Sitagliptin | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Major Hypoglycemia | 0.00 rate per subject-year | Standard Error 0 |
| Sitagliptin | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Minor Hypoglycemia | 0.12 rate per subject-year | Standard Error 0.039 |
| Pioglitazone | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Major Hypoglycemia | 0.00 rate per subject-year | Standard Error 0 |
| Pioglitazone | Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Treatment-Emergent Minor Hypoglycemia | 0.01 rate per subject-year | Standard Error 0.014 |
Secondary
Change in Body Weight From Baseline to Week 26
Change in body weight from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Body Weight From Baseline to Week 26 | -2.31 kg | Standard Error 0.323 |
| Sitagliptin | Change in Body Weight From Baseline to Week 26 | -0.77 kg | Standard Error 0.322 |
| Pioglitazone | Change in Body Weight From Baseline to Week 26 | 2.79 kg | Standard Error 0.32 |
Comparison: Analysis: Change in body weight from baseline (Day 1) to Week 26 was analyzed by an analysis of covariance (ANCOVA) model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of body weight as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.000295% CI: [0.72, 2.35]ANCOVA
Comparison: Analysis: Change in body weight from baseline (Day 1) to Week 26 was analyzed by an analysis of covariance (ANCOVA) model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of body weight as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: <0.000195% CI: [4.28, 5.91]ANCOVA
Secondary
Change in Diastolic Blood Pressure From Baseline to Week 26
Change in diastolic blood pressure from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Diastolic Blood Pressure From Baseline to Week 26 | -1.4 mmHg | Standard Error 0.57 |
| Sitagliptin | Change in Diastolic Blood Pressure From Baseline to Week 26 | -0.4 mmHg | Standard Error 0.57 |
| Pioglitazone | Change in Diastolic Blood Pressure From Baseline to Week 26 | -2.5 mmHg | Standard Error 0.56 |
Comparison: Analysis: Change in diastolic blood pressure from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of diastolic blood pressure as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.168595% CI: [-0.4, 2.5]ANCOVA
Comparison: Analysis: Change in diastolic blood pressure from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of diastolic blood pressure as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.168595% CI: [-2.6, 0.4]ANCOVA
Secondary
Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26
Change in fasting HDL from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 | 2.0 mg/dL | Standard Error 0.61 |
| Sitagliptin | Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 | 2.0 mg/dL | Standard Error 0.6 |
| Pioglitazone | Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 | 6.2 mg/dL | Standard Error 0.59 |
Comparison: Analysis: Change in fasting HDL from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting HDL as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.954695% CI: [-1.6, 1.5]ANCOVA
Comparison: Analysis: Change in fasting HDL from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting HDL as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: <0.000195% CI: [2.6, 5.7]ANCOVA
Secondary
Change in Fasting Plasma Glucose From Baseline to Week 26
Change in fasting plasma glucose from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting Plasma Glucose From Baseline to Week 26 | -31.8 mg/dL | Standard Error 3.79 |
| Sitagliptin | Change in Fasting Plasma Glucose From Baseline to Week 26 | -16.3 mg/dL | Standard Error 3.72 |
| Pioglitazone | Change in Fasting Plasma Glucose From Baseline to Week 26 | -27.3 mg/dL | Standard Error 3.75 |
Comparison: Analysis: Change in fasting plasma glucose from baseline (Day 1) to Week 26 was analyzed using an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting plasma glucose as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.003895% CI: [5.7, 25.2]ANCOVA
Comparison: Analysis: Change in fasting plasma glucose from baseline (Day 1) to Week 26 was analyzed using an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting plasma glucose as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.372995% CI: [-5.3, 14.2]ANCOVA
Secondary
Change in Fasting Total Cholesterol From Baseline to Week 26
Change in fasting total cholesterol from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting Total Cholesterol From Baseline to Week 26 | -0.6 mg/dL | Standard Error 2.51 |
| Sitagliptin | Change in Fasting Total Cholesterol From Baseline to Week 26 | 3.1 mg/dL | Standard Error 2.49 |
| Pioglitazone | Change in Fasting Total Cholesterol From Baseline to Week 26 | 6.2 mg/dL | Standard Error 2.46 |
Comparison: Analysis: Change in fasting total cholesterol from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting total cholesterol as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.268695% CI: [-2.8, 10.2]ANCOVA
Comparison: Analysis: Change in fasting total cholesterol from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting total cholesterol as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.081495% CI: [0.3, 13.2]ANCOVA
Secondary
Change in Systolic Blood Pressure From Baseline to Week 26
Change in systolic blood pressure from baseline (Day 1) to Week 26.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Systolic Blood Pressure From Baseline to Week 26 | -3.6 mmHg | Standard Error 0.97 |
| Sitagliptin | Change in Systolic Blood Pressure From Baseline to Week 26 | 0.2 mmHg | Standard Error 0.95 |
| Pioglitazone | Change in Systolic Blood Pressure From Baseline to Week 26 | -1.6 mmHg | Standard Error 0.95 |
Comparison: Analysis: Change in systolic blood pressure from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of systolic blood pressure as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.005595% CI: [1.3, 6.3]ANCOVA
Comparison: Analysis: Change in systolic blood pressure from baseline (Day 1) to Week 26 was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of systolic blood pressure as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.111795% CI: [-0.5, 4.5]ANCOVA
Secondary
Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26
Percentages of subjects achieving HbA1c target values of \<=6.0% at Week 26.
Time frame: Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 | 13.8 percentage of subjects |
| Sitagliptin | Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 | 9.0 percentage of subjects |
| Pioglitazone | Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 | 4.8 percentage of subjects |
Comparison: Analysis: Percentages of subjects achieving HbA1c target of \<=6.0% at Week 26 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.17Cochran-Mantel-Haenszel
Comparison: Analysis: Percentages of subjects achieving HbA1c target of \<=6.0% at Week 26 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.0091Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26
Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 26.
Time frame: Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 | 38.8 percentage of subjects |
| Sitagliptin | Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 | 15.7 percentage of subjects |
| Pioglitazone | Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 | 26.7 percentage of subjects |
Comparison: Analysis: Percentages of subjects achieving HbA1c target of \<=6.5% at Week 26 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Analysis: Percentages of subjects achieving HbA1c target of \<=6.5% at Week 26 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.012Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving HbA1c Target of <7% at Week 26
Percentages of subjects achieving HbA1c target values of \<7% at Week 26.
Time frame: Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 | 58.8 percentage of subjects |
| Sitagliptin | Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 | 30.7 percentage of subjects |
| Pioglitazone | Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 | 43.6 percentage of subjects |
Comparison: Analysis: Percentage of subjects achieving HbA1c target of \<7% at Week 26 were compared between treatments using a Cochran Mantel Haenszel (CMH) test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Analysis: Percentage of subjects achieving HbA1c target of \<7% at Week 26 were compared between treatments using a Cochran Mantel Haenszel (CMH) test, in which baseline HbA1c stratum (\<9% or \>=9%) and country served as stratification factors. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.0015Cochran-Mantel-Haenszel
Secondary
Ratio of Fasting Triglycerides at Week 26 to Baseline
Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Time frame: Day 1, Week 26
Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.95 ratio | Standard Error 0.029 |
| Sitagliptin | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.95 ratio | Standard Error 0.028 |
| Pioglitazone | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.84 ratio | Standard Error 0.025 |
Comparison: Analysis: Triglycerides data were logarithm-transformed and the change at Week 26 to baseline (Day 1), expressed as the ratio, was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting triglycerides as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.971895% CI: [0.93, 1.08]ANCOVA
Comparison: Analysis: Triglycerides data were logarithm-transformed and the change at Week 26 to baseline (Day 1), expressed as the ratio, was analyzed by an ANCOVA model including treatment, country, and baseline HbA1c stratum (\<9.0% or \>=9.0%) as factors, and baseline value of fasting triglycerides as a covariate. Null hypothesis: no difference across treatments. Power: based on the primary measurement.p-value: 0.006295% CI: [0.82, 0.96]ANCOVA