Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes, exenatide once weekly, Byetta, Amylin, Lilly, Bydureon
Brief summary
This study will compare the effects of commercially manufactured exenatide once weekly and exenatide BID in subjects whose type 2 diabetes is managed with diet and exercise alone or with oral antidiabetic medications. The study will examine glycemic control (as measured by HbA1C), safety, and tolerability.
Interventions
subcutaneous injection, 2.0mg, once a week
subcutaneous injection; 5mcg (4 weeks) and 10mcg (20 weeks); twice a day
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has been diagnosed with type 2 diabetes mellitus * Has hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at screening * Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening * Has been treated with diet and exercise alone or in combination with a stable regimen of metformin (MET), a sulfonylurea (SU), a thiazolidinedione (TZD), a combination of metformin and an SU, a combination of metformin and a TZD, or a combination of an SU and a TZD for a minimum of 2 months prior to screening * 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 screening: * Hormone replacement therapy (female subjects) * Oral contraceptives (female subjects) * Antihypertensive agents * Lipid-lowering agents * Thyroid replacement therapy * Antidepressant agents * 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 ever been exposed to exenatide (exenatide once weekly \[exenatide LAR\], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) analog * Has received any investigational drug within one month (or five half-lives of the investigational drug, whichever is greater) of screening * Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications: * Any dipeptidyl peptidase 4 (DPP-4) inhibitor within 3 months prior to screening * Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of screening * Insulin within 2 weeks of screening or for more than 1 week within 3 months of screening * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 24 | Day 1, Week 24 | Change in HbA1c from baseline (Day 1) to Week 24 \[Week 24 - Baseline\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving HbA1c Target of <=6.5% | Week 24 | Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 24. |
| Change in Fasting Plasma Glucose From Baseline to Week 24 | Day 1, Week 24 | Change in fasting plasma glucose from baseline (Day 1) to Week 24. |
| Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL | Week 24 | Percentages of subjects achieving fasting plasma glucose target of \<=126 mg/dL at Week 24. |
| Change in Body Weight From Baseline to Week 24 | Day 1, Week 24 | Change in body weight from baseline (Day 1) to Week 24. |
| Change in Sitting Systolic Blood Pressure From Baseline to Week 24 | Day 1, Week 24 | Change in systolic blood pressure from baseline (Day 1) to Week 24. |
| Percentage of Subjects Achieving HbA1c Target of <7% | Week 24 | Percentages of subjects achieving HbA1c target value of \<7% at Week 24. |
| Change in Total Cholesterol From Baseline to Week 24 | Day 1, Week 24 | Change in total cholesterol from baseline (Day 1) to Week 24. |
| Change in High-density Lipoprotein (HDL) From Baseline to Week 24 | Day 1, Week 24 | Change in HDL from baseline (Day 1) to Week 24. |
| Ratio of Triglycerides at Week 24 to Baseline | Day 1, Week 24 | Ratio of triglycerides (measured in mg/dL) at Week 24 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 Major Hypoglycemic Events | Day 1 to Week 24 | The major hypoglycemia category included 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 of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject. |
| Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | Day 1 to Week 24 | The minor hypoglycemia category included events in which symptoms consistent with hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia. |
| Change in Sitting Diastolic Blood Pressure From Baseline to Week 24 | Day 1, Week 24 | Change in diastolic blood pressure from baseline (Day 1) to Week 24. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Once Weekly Subcutaneous injection of 2 mg exenatide, once a week | 129 |
| Exenatide Twice Daily Subcutaneous injection of exenatide, twice a day (5 mcg exenatide per dose for first 4 weeks, then 10 mcg exenatide per dose for 20 weeks) | 123 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 |
| Overall Study | Investigator Decision | 0 | 2 |
| Overall Study | Loss of Glucose Control | 3 | 4 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal of Consent | 6 | 12 |
Baseline characteristics
| Characteristic | Exenatide Once Weekly | Exenatide Twice Daily | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 26 Participants | 21 Participants | 47 Participants |
| Age, Categorical Between 18 and 65 years | 103 Participants | 102 Participants | 205 Participants |
| Age, Continuous | 56.1 years STANDARD_DEVIATION 11.14 | 55.2 years STANDARD_DEVIATION 10.27 | 55.7 years STANDARD_DEVIATION 10.71 |
| Background Oral Antidiabetic Agent Diet and Exercise | 21 participants | 26 participants | 47 participants |
| Background Oral Antidiabetic Agent Metformin (MET) | 51 participants | 52 participants | 103 participants |
| Background Oral Antidiabetic Agent MET+SU | 34 participants | 25 participants | 59 participants |
| Background Oral Antidiabetic Agent MET+TZD | 13 participants | 9 participants | 22 participants |
| Background Oral Antidiabetic Agent Sulfonylurea (SU) | 1 participants | 8 participants | 9 participants |
| Background Oral Antidiabetic Agent SU+MET+TZD | 5 participants | 1 participants | 6 participants |
| Background Oral Antidiabetic Agent Thiazolidinediones (TZD) | 4 participants | 2 participants | 6 participants |
| Glycosylated hemoglobin (HbA1c) | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.1 | 8.4 percentage of total hemoglobin STANDARD_DEVIATION 1.23 | 8.4 percentage of total hemoglobin STANDARD_DEVIATION 1.16 |
| Sex: Female, Male Female | 52 Participants | 55 Participants | 107 Participants |
| Sex: Female, Male Male | 77 Participants | 68 Participants | 145 Participants |
| Weight | 97.0 kg STANDARD_DEVIATION 20.66 | 94.3 kg STANDARD_DEVIATION 18.94 | 95.7 kg STANDARD_DEVIATION 19.85 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 129 | 58 / 123 |
| serious Total, serious adverse events | 3 / 129 | 5 / 123 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 24
Change in HbA1c from baseline (Day 1) to Week 24 \[Week 24 - Baseline\].
Time frame: Day 1, Week 24
Population: The ITT Population consisted of all randomized subjects who received at least one injection of study medication. Missing data up to Week 24 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 24 | -1.57 percentage of total hemoglobin | Standard Error 0.104 |
| Exenatide Twice Daily | Change in HbA1c From Baseline to Week 24 | -0.90 percentage of total hemoglobin | Standard Error 0.11 |
Comparison: Superiority of exenatide once weekly to BYETTA if the upper limit of the 2-sided 95% CI for treatment difference (exenatide once weekly minus BYETTA) is \<0; noninferiority if this upper limit is \<0.4%. Power: Assuming 15% dropout rate with 206 subjects will complete the study. This sample size would provide 90% power for non-inferiority test with assumption of greater reduction (0.1%) in exenatide once weekly and a common standard deviation of 1.1%.p-value: <0.000195% CI: [-0.94, -0.39]ANOVA
Secondary
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
The major hypoglycemia category included 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 of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject.
Time frame: Day 1 to Week 24
Population: ITT Population. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
| Exenatide Twice Daily | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
| Exenatide Once Weekly No SU | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
| Exenatide Twice Daily No SU | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
Secondary
Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
The minor hypoglycemia category included events in which symptoms consistent with hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Time frame: Day 1 to Week 24
Population: ITT Population. Analysis was done for SU ITT patients (ITT patients taking SU) and Non-SU ITT patients separately.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | 0.75 rate per subject-year | Standard Error 0.217 |
| Exenatide Twice Daily | Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | 0.31 rate per subject-year | Standard Error 0.153 |
| Exenatide Once Weekly No SU | Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
| Exenatide Twice Daily No SU | Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | 0.00 rate per subject-year | Standard Error 0 |
Secondary
Change in Body Weight From Baseline to Week 24
Change in body weight from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 24 | -2.33 kg | Standard Error 0.369 |
| Exenatide Twice Daily | Change in Body Weight From Baseline to Week 24 | -1.37 kg | Standard Error 0.386 |
Comparison: Analysis: Change in body weight from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the body weight as a covariate. Null hypothesis: no difference between treatments in change from baseline body weight. Power: based on the primary measurement.p-value: 0.051495% CI: [-1.91, 0.01]ANCOVA
Secondary
Change in Fasting Plasma Glucose From Baseline to Week 24
Change in fasting plasma glucose from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 24 | -25.1 mg/dL | Standard Error 4.32 |
| Exenatide Twice Daily | Change in Fasting Plasma Glucose From Baseline to Week 24 | -4.6 mg/dL | Standard Error 4.5 |
Comparison: Analysis: Change in fasting plasma glucose from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the fasting plasma glucose as a covariate. Null hypothesis: no difference between treatments in change from baseline fasting plasma glucose. Power: based on the primary measurement.p-value: 0.000695% CI: [-31.4, -9.5]ANCOVA
Secondary
Change in High-density Lipoprotein (HDL) From Baseline to Week 24
Change in HDL from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 High-density Lipoprotein (HDL) From Baseline to Week 24 | 0.0 mg/dL | Standard Error 0.6 |
| Exenatide Twice Daily | Change in High-density Lipoprotein (HDL) From Baseline to Week 24 | 1.3 mg/dL | Standard Error 0.64 |
Comparison: Analysis: Change in HDL from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the HDL as a covariate. Null hypothesis: no difference between treatments in change from baseline HDL. Power: based on the primary measurement.p-value: 0.125195% CI: [-2.8, 0.3]ANCOVA
Secondary
Change in Sitting Diastolic Blood Pressure From Baseline to Week 24
Change in diastolic blood pressure from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 Sitting Diastolic Blood Pressure From Baseline to Week 24 | 0.2 mmHg | Standard Error 0.74 |
| Exenatide Twice Daily | Change in Sitting Diastolic Blood Pressure From Baseline to Week 24 | -0.1 mmHg | Standard Error 0.78 |
Comparison: Analysis: Change in diastolic blood pressure from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the diastolic blood pressure as a covariate. Null hypothesis: no difference between treatments in change from baseline diastolic blood pressure. Power: based on the primary measurement.p-value: 0.771795% CI: [-1.7, 2.2]ANCOVA
Secondary
Change in Sitting Systolic Blood Pressure From Baseline to Week 24
Change in systolic blood pressure from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 Sitting Systolic Blood Pressure From Baseline to Week 24 | -2.9 mmHg | Standard Error 1.13 |
| Exenatide Twice Daily | Change in Sitting Systolic Blood Pressure From Baseline to Week 24 | -1.2 mmHg | Standard Error 1.19 |
Comparison: Analysis: Change in systolic blood pressure from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the systolic blood pressure as a covariate. Null hypothesis: no difference between treatments in change from baseline systolic blood pressure. Power: based on the primary measurement.p-value: 0.236795% CI: [-4.7, 1.2]ANCOVA
Secondary
Change in Total Cholesterol From Baseline to Week 24
Change in total cholesterol from baseline (Day 1) to Week 24.
Time frame: Day 1, Week 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 Total Cholesterol From Baseline to Week 24 | -15.4 mg/dL | Standard Error 2.61 |
| Exenatide Twice Daily | Change in Total Cholesterol From Baseline to Week 24 | 0.6 mg/dL | Standard Error 2.79 |
Comparison: Analysis: Change in total cholesterol from baseline (Day 1) to Week 24 was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the total cholesterol as a covariate. Null hypothesis: no difference between treatments in change from baseline total cholesterol. Power: based on the primary measurement.p-value: <0.000195% CI: [-22.9, -9.1]ANCOVA
Secondary
Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL
Percentages of subjects achieving fasting plasma glucose target of \<=126 mg/dL at Week 24.
Time frame: Week 24
Population: ITT Population. Missing data up to Week 24 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 measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL | 50.4 percentage of subjects |
| Exenatide Twice Daily | Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL | 30.9 percentage of subjects |
Comparison: Analysis: Percentages of subjects achieving fasting plasma glucose target of \<=126 mg/dL at Week 24 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving fasting plasma glucose target. Power: based on the primary measurement.p-value: 0.0008Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving HbA1c Target of <=6.5%
Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 24.
Time frame: Week 24
Population: ITT Population. Missing data up to Week 24 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 measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving HbA1c Target of <=6.5% | 41.1 percentage of subjects |
| Exenatide Twice Daily | Percentage of Subjects Achieving HbA1c Target of <=6.5% | 16.3 percentage of subjects |
Comparison: Analysis: Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 24 were compared between treatments using a CMH test, in which baseline HbA1c stratum (\<9% or \>=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving HbA1c target. Power: based on the primary measurement.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Achieving HbA1c Target of <7%
Percentages of subjects achieving HbA1c target value of \<7% at Week 24.
Time frame: Week 24
Population: ITT Population. Missing data up to Week 24 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 measurement were categorized as not achieving goal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Subjects Achieving HbA1c Target of <7% | 58.1 percentage of subjects |
| Exenatide Twice Daily | Percentage of Subjects Achieving HbA1c Target of <7% | 30.1 percentage of subjects |
Comparison: Analysis: Percentages of subjects achieving HbA1c target value of \<7% at Week 24 were compared between treatments using a Cochran-Mantel-Haenszel (CMH) test, in which baseline HbA1c stratum (\<9% or \>=9%) and concomitant SU use at screening served as the stratification factors. Null hypothesis: no difference between treatments in percentage of subjects achieving HbA1c target. Power: based on the primary measurement.p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Ratio of Triglycerides at Week 24 to Baseline
Ratio of triglycerides (measured in mg/dL) at Week 24 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 24
Population: ITT Population. Missing data up to Week 24 were imputed using 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 Triglycerides at Week 24 to Baseline | 0.94 ratio | Standard Error 0.032 |
| Exenatide Twice Daily | Ratio of Triglycerides at Week 24 to Baseline | 0.99 ratio | Standard Error 0.036 |
Comparison: Analysis: Triglycerides data were logarithm-transformed and the change at Week 30 to baseline (Day 1) , expressed as the ratio, was analyzed by an ANCOVA model including treatment, baseline HbA1c stratum (\<9% or \>=9%), and concomitant SU use at screening as factors, and baseline value of the triglycerides as a covariate. Null hypothesis: no difference between treatments in change from baseline triglycerides. Power: based on the primary measurement.p-value: 0.255895% CI: [0.87, 1.04]ANCOVA