Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, exenatide, rosiglitazone, Amylin, Lilly
Brief summary
This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control.
Interventions
DRUGexenatide
subcutaneous injection, 5mcg or 10mcg, twice a day
DRUGrosiglitazone
oral tablet, 2mg or 4mg, 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 75 Years
Healthy volunteers
No
Inclusion criteria
* HbA1c of 6.8% to 10.0%, inclusive. * Body mass index (BMI) of 25 kg/m\^2 to 40 kg/m\^2, inclusive.
Exclusion criteria
* Have participated in this study previously, or have received exenatide, pramlintide acetate, GLP-1 analogs, or dipeptidyl peptidase-IV (DPP-IV) inhibitors * Have participated in an interventional, medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of study start. This criterion includes drugs that have not received regulatory approval for any indication at the time of study start. * Treated with any of the following medications: * Thiazolidinedione within 5 months of screening; * Sulfonylurea within 3 months of screening; * Metformin/sulfonylurea combination therapy within 3 months of screening; * Alpha-glucosidase inhibitor within 3 months of screening; * Meglitinide within 3 months of screening; * Insulin for more than 1 week within the 3 months prior to screening. * Symlin (pramlintide acetate) injection or Byetta (exenatide) injection at any time * Chronic (more than 2 weeks) or recent (within 4 weeks of study start) use of a drug that directly affects gastrointestinal motility * Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding study start * Regular use of a medication with addictive potential such as an opiate, narcotic, or tranquilizer * Systemic antineoplastic agent * Systemic transplantation medication * Drugs for weight loss, including over-the-counter medications, within the 4 months prior to study start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ASIiAUC During a Hyperglycemic Clamp Test. | 20 weeks | Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hip Circumference | 20 weeks | Change in hip circumference form baseline to week 20 |
| Change in Waist-to-hip Ratio | 20 weeks | Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20 |
| Incidence of Hypoglycemia Events | 20 weeks | Number of subjects experiencing hypoglycemia at any point during the study |
| Hypoglycemia Rate Per 30 Days Per Patient | 20 weeks | Average number of episodes of hypoglycemia per 30 days per patient |
| Change in AUC for Glucose During a Meal Challenge Test (MCT). | Week 20 | Change in AUC(15-180 min) for glucose during a MCT baseline to week 20. |
| Change in Insulin Sensitivity Index as Measured by M-value. | Week 20 | Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20. |
| Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Week 20 | Change in insulin AUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test. |
| Change in Insulin iAUC From Baseline to Endpoint. | Week 20 | Change in insulin iAUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test. |
| Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Week 20 | Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT. |
| Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Week 20 | Ratio (value at endpoint divided by value at baseline) of AUC(15-180 min) for C-peptide (nmol-min/L) during a MCT from baseline to week 20. |
| Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Week 20 | Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20. |
| Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Week 20 | Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20. |
| Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Week 20 | Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20. |
| Change in HbA1c | Week 20 | Change in HbA1c from baseline to week 20. |
| Change in Fasting Serum Glucose Concentration. | Week 20 | Change in fasting serum glucose concentration from baseline to week 20. |
| Change in Fasting C-peptide | Week 20 | Change in fasting C-peptide from baseline to week 20. |
| Change in Fasting Insulin | Week 20 | Change in fasting insulin from baseline to week 20. |
| Change in Fasting Proinsulin | Week 20 | Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline |
| Change in Body Weight | Week 20 | Change in body weight from baseline to week 20. |
| Change in Fasting Total Cholesterol. | Week 20 | Change in fasting total cholestrol from baseline to week 20. |
| Change in Fasting HDL Cholesterol | Week 20 | Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20. |
| Change in Fasting LDL Cholesterol | Week 20 | Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20. |
| Change in Fasting Triglycerides | Week 20 | Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20. |
| Change in Percent Body Fat During a Meal Challenge Test (MCT) | 20 weeks | Change in percent body fat from baseline to week 20, as assessed during an MCT |
| Change in Body Fat Mass During a Meal Challenge Test (MCT) | 20 weeks | Change in body fat mass form baseline to week 20, as assessed during an MCT |
| Change in Lean Body Mass During a Meal Challenge Test (MCT) | 20 weeks | Change in lean body mass from baseline to week 20, as assessed during an MCT |
| Change in Waist Circumference | 20 weeks | Change in waist circumference from baseline to week 20 |
| Pedal Edema Score | 20 weeks | Pedal edema scores experienced by each patient throughout the study (1+ indicates a patient experienced a pedal edema score of 1 , 2, or 3; 2+ indicates a patient experienced a pedal edema score of 2 or 3, etc.) Scale: 1. Slight pitting, no visible distortion, disappears rapidly 2. A somewhat deeper pit than in 1+, but again no readily detectable distortion, and it disappears in 10 - 15 seconds 3. The pit is noticeably deep and may last more than a minute; the dependent extremity looks fuller and swollen 4. The pit is very deep, lasts as long as 2 - 5 minutes, and the dependent extremity is grossly distorted |
Countries
United States
Participant flow
Recruitment details
Enrollment occurred between 18 October 2005 and 14 March 2008.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Exenatide 5 mcg twice a day (BID) for 4-weeks followed by exenatide 10 mcg BID for 16-weeks. | 45 |
| Exenatide Plus Rosiglitazone Exenatide 5 mcg BID + rosiglitazone 2 mg BID for 4-weeks followed by exenatide 10 mcg + rosiglitazone 4 mg BID for 16-weeks. | 47 |
| Rosiglitazone Rosiglitazone 2 mg BID for 4-weeks followed by rosiglitazone 4 mgs BID for 16-weeks. | 45 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 3 |
| Overall Study | Patient Decision | 5 | 1 | 4 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 3 | 3 |
| Overall Study | Sponsor Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Exenatide | Exenatide Plus Rosiglitazone | Rosiglitazone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 10 Participants | 9 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 37 Participants | 36 Participants | 109 Participants |
| Age, Continuous | 56.99 years STANDARD_DEVIATION 9.71 | 54.63 years STANDARD_DEVIATION 9.91 | 55.54 years STANDARD_DEVIATION 10.71 | 55.70 years STANDARD_DEVIATION 10.09 |
| Sex: Female, Male Female | 22 Participants | 25 Participants | 20 Participants | 67 Participants |
| Sex: Female, Male Male | 23 Participants | 22 Participants | 25 Participants | 70 Participants |
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 | 35 / — | 41 / — | 33 / — |
| serious Total, serious adverse events | 3 / — | 4 / — | 4 / — |
Outcome results
Primary
Change in ASIiAUC During a Hyperglycemic Clamp Test.
Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function.
Time frame: 20 weeks
Population: All patients in full analysis set who participated in clamp test and have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Baseline ASIiAUC | 643.40 uIU-min/ml | Standard Error 106.71 |
| Exenatide | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Change in ASIiAUC at week 20 | 747.26 uIU-min/ml | Standard Error 187.4 |
| Exenatide Plus Rosiglitazone | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Baseline ASIiAUC | 686.41 uIU-min/ml | Standard Error 103.7 |
| Exenatide Plus Rosiglitazone | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Change in ASIiAUC at week 20 | 194.68 uIU-min/ml | Standard Error 181.59 |
| Rosiglitazone | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Baseline ASIiAUC | 786.12 uIU-min/ml | Standard Error 113.6 |
| Rosiglitazone | Change in ASIiAUC During a Hyperglycemic Clamp Test. | Change in ASIiAUC at week 20 | -99.85 uIU-min/ml | Standard Error 200.04 |
Comparison: The ratio of the ASI-iAUC at Week 20 to that at baseline was compared between the treatment groups.p-value: 0.282ANCOVA
Secondary
Change in AUC for C-peptide During a Meal Challenge Test (MCT).
Ratio (value at endpoint divided by value at baseline) of AUC(15-180 min) for C-peptide (nmol-min/L) during a MCT from baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Baseline C-peptide during a MCT | 319.77 nmol-min/L | Standard Error 18.13 |
| Exenatide | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of C-peptide during a MCT | 0.908 nmol-min/L | Standard Error 0.04 |
| Exenatide Plus Rosiglitazone | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Baseline C-peptide during a MCT | 310.51 nmol-min/L | Standard Error 17.61 |
| Exenatide Plus Rosiglitazone | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of C-peptide during a MCT | 0.804 nmol-min/L | Standard Error 0.036 |
| Rosiglitazone | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Baseline C-peptide during a MCT | 325.65 nmol-min/L | Standard Error 19.04 |
| Rosiglitazone | Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of C-peptide during a MCT | 0.854 nmol-min/L | Standard Error 0.039 |
p-value: 0.348ANCOVA
Secondary
Change in AUC for Glucose During a Meal Challenge Test (MCT).
Change in AUC(15-180 min) for glucose during a MCT baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Baseline glucose AUC during MCT | 1782.86 mmol-min/L | Standard Error 60.47 |
| Exenatide | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Change in glucose AUC during MCT at week 20 | -560.12 mmol-min/L | Standard Error 50.95 |
| Exenatide Plus Rosiglitazone | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Baseline glucose AUC during MCT | 1799.68 mmol-min/L | Standard Error 59.6 |
| Exenatide Plus Rosiglitazone | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Change in glucose AUC during MCT at week 20 | -635.24 mmol-min/L | Standard Error 50.25 |
| Rosiglitazone | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Baseline glucose AUC during MCT | 1741.87 mmol-min/L | Standard Error 60.47 |
| Rosiglitazone | Change in AUC for Glucose During a Meal Challenge Test (MCT). | Change in glucose AUC during MCT at week 20 | -425.59 mmol-min/L | Standard Error 51.02 |
p-value: 0.004ANCOVA
Secondary
Change in Body Fat Mass During a Meal Challenge Test (MCT)
Change in body fat mass form baseline to week 20, as assessed during an MCT
Time frame: 20 weeks
Population: All Patients in Full Analysis Set Who Have Both Baseline and Endpoint Measurements
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Baseline body fat mass | 32.05 kg | Standard Error 1.64 |
| Exenatide | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Change in body fat mass at week 20 | -2.76 kg | Standard Error 1.37 |
| Exenatide Plus Rosiglitazone | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Baseline body fat mass | 32.55 kg | Standard Error 1.62 |
| Exenatide Plus Rosiglitazone | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Change in body fat mass at week 20 | -1.06 kg | Standard Error 1.35 |
| Rosiglitazone | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Baseline body fat mass | 30.54 kg | Standard Error 1.67 |
| Rosiglitazone | Change in Body Fat Mass During a Meal Challenge Test (MCT) | Change in body fat mass at week 20 | -1.99 kg | Standard Error 1.4 |
p-value: 0.631ANCOVA
Secondary
Change in Body Weight
Change in body weight from baseline to week 20.
Time frame: Week 20
Population: All patients who aave both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Body Weight | Baseline body weight | 93.05 kg | Standard Error 2.39 |
| Exenatide | Change in Body Weight | Change in body weight at week 20 | -2.82 kg | Standard Error 0.547 |
| Exenatide Plus Rosiglitazone | Change in Body Weight | Baseline body weight | 93.76 kg | Standard Error 2.36 |
| Exenatide Plus Rosiglitazone | Change in Body Weight | Change in body weight at week 20 | -1.21 kg | Standard Error 0.538 |
| Rosiglitazone | Change in Body Weight | Baseline body weight | 91.78 kg | Standard Error 2.39 |
| Rosiglitazone | Change in Body Weight | Change in body weight at week 20 | 1.48 kg | Standard Error 0.547 |
p-value: <0.001MMRM
Secondary
Change in Fasting C-peptide
Change in fasting C-peptide from baseline to week 20.
Time frame: Week 20
Population: Fasting C-peptide was initially identified as an outcome measure, but data for this measure were not subsequently collected at baseline or endpoint.
Secondary
Change in Fasting HDL Cholesterol
Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting HDL Cholesterol | Baseline HDL | 1.13 mmol/L | Standard Error 0.048 |
| Exenatide | Change in Fasting HDL Cholesterol | Change from baseline HDL at week 20 | 0.022 mmol/L | Standard Error 0.03 |
| Exenatide Plus Rosiglitazone | Change in Fasting HDL Cholesterol | Baseline HDL | 1.17 mmol/L | Standard Error 0.047 |
| Exenatide Plus Rosiglitazone | Change in Fasting HDL Cholesterol | Change from baseline HDL at week 20 | 0.046 mmol/L | Standard Error 0.029 |
| Rosiglitazone | Change in Fasting HDL Cholesterol | Baseline HDL | 1.17 mmol/L | Standard Error 0.048 |
| Rosiglitazone | Change in Fasting HDL Cholesterol | Change from baseline HDL at week 20 | 0.055 mmol/L | Standard Error 0.03 |
p-value: 0.84MMRM
Secondary
Change in Fasting Insulin
Change in fasting insulin from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting Insulin | Baseline fasting insulin | 12.84 uIU/ml | Standard Error 1.55 |
| Exenatide | Change in Fasting Insulin | Ratio (wk20/baseline)of fasting insulin | 0.980 uIU/ml | Standard Error 0.096 |
| Exenatide Plus Rosiglitazone | Change in Fasting Insulin | Baseline fasting insulin | 10.96 uIU/ml | Standard Error 1.33 |
| Exenatide Plus Rosiglitazone | Change in Fasting Insulin | Ratio (wk20/baseline)of fasting insulin | 0.599 uIU/ml | Standard Error 0.059 |
| Rosiglitazone | Change in Fasting Insulin | Baseline fasting insulin | 12.77 uIU/ml | Standard Error 1.54 |
| Rosiglitazone | Change in Fasting Insulin | Ratio (wk20/baseline)of fasting insulin | 0.755 uIU/ml | Standard Error 0.078 |
p-value: 0.106MMRM
Secondary
Change in Fasting LDL Cholesterol
Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting LDL Cholesterol | Baseline LDL | 2.59 mmol/L | Standard Error 0.131 |
| Exenatide | Change in Fasting LDL Cholesterol | Change from baseline LDL at week 20 | -0.049 mmol/L | Standard Error 0.102 |
| Exenatide Plus Rosiglitazone | Change in Fasting LDL Cholesterol | Baseline LDL | 2.57 mmol/L | Standard Error 0.128 |
| Exenatide Plus Rosiglitazone | Change in Fasting LDL Cholesterol | Change from baseline LDL at week 20 | 0.096 mmol/L | Standard Error 0.1 |
| Rosiglitazone | Change in Fasting LDL Cholesterol | Baseline LDL | 2.71 mmol/L | Standard Error 0.129 |
| Rosiglitazone | Change in Fasting LDL Cholesterol | Change from baseline LDL at week 20 | 0.334 mmol/L | Standard Error 0.101 |
p-value: 0.096MMRM
Secondary
Change in Fasting Proinsulin
Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting Proinsulin | Baseline fasting proinsulin | 4.32 pmol/L | Standard Error 0.523 |
| Exenatide | Change in Fasting Proinsulin | Ratio(wk20/baseline)of fasting proinsulin | 0.663 pmol/L | Standard Error 0.073 |
| Exenatide Plus Rosiglitazone | Change in Fasting Proinsulin | Baseline fasting proinsulin | 3.80 pmol/L | Standard Error 0.455 |
| Exenatide Plus Rosiglitazone | Change in Fasting Proinsulin | Ratio(wk20/baseline)of fasting proinsulin | 0.538 pmol/L | Standard Error 0.058 |
| Rosiglitazone | Change in Fasting Proinsulin | Baseline fasting proinsulin | 3.56 pmol/L | Standard Error 0.423 |
| Rosiglitazone | Change in Fasting Proinsulin | Ratio(wk20/baseline)of fasting proinsulin | 0.623 pmol/L | Standard Error 0.068 |
p-value: 0.341MMRM
Secondary
Change in Fasting Serum Glucose Concentration.
Change in fasting serum glucose concentration from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting Serum Glucose Concentration. | Baseline fasting serum glucose | 8.42 mmol/L | Standard Error 0.278 |
| Exenatide | Change in Fasting Serum Glucose Concentration. | Change fr baseline fasting serum glucose at wk 20 | -1.46 mmol/L | Standard Error 0.25 |
| Exenatide Plus Rosiglitazone | Change in Fasting Serum Glucose Concentration. | Baseline fasting serum glucose | 8.43 mmol/L | Standard Error 0.271 |
| Exenatide Plus Rosiglitazone | Change in Fasting Serum Glucose Concentration. | Change fr baseline fasting serum glucose at wk 20 | -1.60 mmol/L | Standard Error 0.244 |
| Rosiglitazone | Change in Fasting Serum Glucose Concentration. | Baseline fasting serum glucose | 8.48 mmol/L | Standard Error 0.274 |
| Rosiglitazone | Change in Fasting Serum Glucose Concentration. | Change fr baseline fasting serum glucose at wk 20 | -1.80 mmol/L | Standard Error 0.25 |
p-value: 0.555MMRM
Secondary
Change in Fasting Total Cholesterol.
Change in fasting total cholestrol from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting Total Cholesterol. | Change fr baseline total cholesterol at week 20 | -0.128 mmol/L | Standard Error 0.118 |
| Exenatide | Change in Fasting Total Cholesterol. | Baseline total cholesterol | 4.42 mmol/L | Standard Error 0.15 |
| Exenatide Plus Rosiglitazone | Change in Fasting Total Cholesterol. | Baseline total cholesterol | 4.41 mmol/L | Standard Error 0.145 |
| Exenatide Plus Rosiglitazone | Change in Fasting Total Cholesterol. | Change fr baseline total cholesterol at week 20 | 0.258 mmol/L | Standard Error 0.114 |
| Rosiglitazone | Change in Fasting Total Cholesterol. | Baseline total cholesterol | 4.62 mmol/L | Standard Error 0.149 |
| Rosiglitazone | Change in Fasting Total Cholesterol. | Change fr baseline total cholesterol at week 20 | 0.438 mmol/L | Standard Error 0.118 |
p-value: 0.276MMRM
Secondary
Change in Fasting Triglycerides
Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Fasting Triglycerides | Baseline triglyceride | 1.56 mmol/L | Standard Error 0.124 |
| Exenatide | Change in Fasting Triglycerides | Ratio (endpoint/baseline) for triglycerides | 0.861 mmol/L | Standard Error 0.06 |
| Exenatide Plus Rosiglitazone | Change in Fasting Triglycerides | Baseline triglyceride | 1.67 mmol/L | Standard Error 0.128 |
| Exenatide Plus Rosiglitazone | Change in Fasting Triglycerides | Ratio (endpoint/baseline) for triglycerides | 0.977 mmol/L | Standard Error 0.066 |
| Rosiglitazone | Change in Fasting Triglycerides | Baseline triglyceride | 1.76 mmol/L | Standard Error 0.138 |
| Rosiglitazone | Change in Fasting Triglycerides | Ratio (endpoint/baseline) for triglycerides | 0.992 mmol/L | Standard Error 0.069 |
p-value: 0.875MMRM
Secondary
Change in HbA1c
Change in HbA1c from baseline to week 20.
Time frame: Week 20
Population: All patients who have both baseline and at least one post baseline value in full analysis set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in HbA1c | Change from baseline HbA1c at week 20 | -0.908 Percentage | Standard Error 0.118 |
| Exenatide | Change in HbA1c | Baseline HbA1c | 7.79 Percentage | Standard Error 0.116 |
| Exenatide Plus Rosiglitazone | Change in HbA1c | Baseline HbA1c | 7.84 Percentage | Standard Error 0.115 |
| Exenatide Plus Rosiglitazone | Change in HbA1c | Change from baseline HbA1c at week 20 | -1.31 Percentage | Standard Error 0.116 |
| Rosiglitazone | Change in HbA1c | Baseline HbA1c | 7.92 Percentage | Standard Error 0.116 |
| Rosiglitazone | Change in HbA1c | Change from baseline HbA1c at week 20 | -0.968 Percentage | Standard Error 0.118 |
p-value: 0.039Mixed Model Repeated Measures (MMRM)
Secondary
Change in Hip Circumference
Change in hip circumference form baseline to week 20
Time frame: 20 weeks
Population: All Patients Who Have Both Baseline and At Least One Post Baseline Value in Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Hip Circumference | Baseline hip circumference | 113.29 cm | Standard Error 1.71 |
| Exenatide | Change in Hip Circumference | Change in hip circumference at week 20 | -1.28 cm | Standard Error 0.848 |
| Exenatide Plus Rosiglitazone | Change in Hip Circumference | Baseline hip circumference | 112.12 cm | Standard Error 1.69 |
| Exenatide Plus Rosiglitazone | Change in Hip Circumference | Change in hip circumference at week 20 | 0.147 cm | Standard Error 0.827 |
| Rosiglitazone | Change in Hip Circumference | Baseline hip circumference | 111.90 cm | Standard Error 1.69 |
| Rosiglitazone | Change in Hip Circumference | Change in hip circumference at week 20 | 1.51 cm | Standard Error 0.838 |
p-value: 0.251MMRM
Secondary
Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT).
Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who have baseline and endpoint measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 120 min at week 20 | -0.259 mmol/L | Standard Error 0.1 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 60 min at week 20 | -0.148 mmol/L | Standard Error 0.09 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 15 min at week 20 | -0.006 mmol/L | Standard Error 0.045 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 120 min | 0.817 mmol/L | Standard Error 0.112 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 90 min | 0.895 mmol/L | Standard Error 0.1 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 30 min | 0.521 mmol/L | Standard Error 0.059 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 90 min at week 20 | -0.185 mmol/L | Standard Error 0.099 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 15 min | 0.238 mmol/L | Standard Error 0.049 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 150 min at week 20 | -0.251 mmol/L | Standard Error 0.095 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 30 min at week 20 | -0.071 mmol/L | Standard Error 0.056 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 180 min at week 20 | -0.075 mmol/L | Standard Error 0.062 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 150 min | 0.843 mmol/L | Standard Error 0.091 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 60 min | 0.818 mmol/L | Standard Error 0.11 |
| Exenatide | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 180 min | 0.610 mmol/L | Standard Error 0.084 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 150 min | 0.651 mmol/L | Standard Error 0.091 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 15 min | 0.259 mmol/L | Standard Error 0.049 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 30 min | 0.517 mmol/L | Standard Error 0.059 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 30 min at week 20 | -0.036 mmol/L | Standard Error 0.056 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 60 min | 0.871 mmol/L | Standard Error 0.11 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 60 min at week 20 | -0.025 mmol/L | Standard Error 0.09 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 90 min | 0.953 mmol/L | Standard Error 0.101 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 90 min at week 20 | -0.117 mmol/L | Standard Error 0.101 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 120 min | 0.828 mmol/L | Standard Error 0.114 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 120 min at week 20 | -0.134 mmol/L | Standard Error 0.102 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 15 min at week 20 | 0.016 mmol/L | Standard Error 0.046 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 150 min at week 20 | -0.254 mmol/L | Standard Error 0.095 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 180 min | 0.482 mmol/L | Standard Error 0.085 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 180 min at week 20 | -0.238 mmol/L | Standard Error 0.063 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 180 min at week 20 | -0.092 mmol/L | Standard Error 0.064 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 120 min at week 20 | -0.016 mmol/L | Standard Error 0.102 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 30 min at week 20 | 0.099 mmol/L | Standard Error 0.058 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 180 min | 0.619 mmol/L | Standard Error 0.087 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 150 min | 0.813 mmol/L | Standard Error 0.092 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 30 min | 0.560 mmol/L | Standard Error 0.061 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 15 min at week 20 | 0.087 mmol/L | Standard Error 0.047 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 90 min | 1.03 mmol/L | Standard Error 0.106 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 150 min at week 20 | -0.093 mmol/L | Standard Error 0.096 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 90 min at week 20 | -0.052 mmol/L | Standard Error 0.106 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change fr baseline C-peptide at 60 min at week 20 | 0.054 mmol/L | Standard Error 0.093 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 15 min | 0.206 mmol/L | Standard Error 0.051 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 120 min | 0.972 mmol/L | Standard Error 0.114 |
| Rosiglitazone | Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Baseline C-peptide at 60 min | 0.881 mmol/L | Standard Error 0.114 |
Secondary
Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT).
Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 15 min | 0.950 mmol/L | Standard Error 0.138 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 120 min at wk 20 | -2.24 mmol/L | Standard Error 0.271 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 60 min at wk 20 | -2.56 mmol/L | Standard Error 0.329 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 180 minutes | 0.461 mmol/L | Standard Error 0.235 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 120 minutes | 2.49 mmol/L | Standard Error 0.235 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 90 minutes | 3.24 mmol/L | Standard Error 0.231 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 30 min | 2.39 mmol/L | Standard Error 0.218 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 90 min at wk 20 | -2.87 mmol/L | Standard Error 0.312 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 180 min at wk 20 | -0.583 mmol/L | Standard Error 0.231 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 150 min at wk 20 | -1.42 mmol/L | Standard Error 0.288 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 30 min at wk 20 | -1.46 mmol/L | Standard Error 0.248 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 15 min at wk 20 | -0.651 mmol/L | Standard Error 0.151 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 150 minutes | 1.62 mmol/L | Standard Error 0.23 |
| Exenatide | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 60 minutes | 3.59 mmol/L | Standard Error 0.273 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 180 min at wk 20 | -0.995 mmol/L | Standard Error 0.232 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 15 min | 1.12 mmol/L | Standard Error 0.138 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 15 min at wk 20 | -0.286 mmol/L | Standard Error 0.152 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 30 min | 2.54 mmol/L | Standard Error 0.221 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 30 min at wk 20 | -1.06 mmol/L | Standard Error 0.252 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 60 minutes | 3.88 mmol/L | Standard Error 0.273 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 60 min at wk 20 | -2.46 mmol/L | Standard Error 0.33 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 90 minutes | 3.36 mmol/L | Standard Error 0.228 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 90 min at wk 20 | -2.91 mmol/L | Standard Error 0.307 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 120 minutes | 2.24 mmol/L | Standard Error 0.238 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 120 min at wk 20 | -2.52 mmol/L | Standard Error 0.275 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 150 minutes | 1.14 mmol/L | Standard Error 0.23 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 150 min at wk 20 | -1.95 mmol/L | Standard Error 0.287 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 180 minutes | 0.036 mmol/L | Standard Error 0.235 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 60 minutes | 3.48 mmol/L | Standard Error 0.273 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 180 min at wk 20 | -0.481 mmol/L | Standard Error 0.23 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 120 min at wk 20 | -0.912 mmol/L | Standard Error 0.271 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 30 min at wk 20 | -0.066 mmol/L | Standard Error 0.252 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 180 minutes | 0.279 mmol/L | Standard Error 0.235 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 150 minutes | 1.25 mmol/L | Standard Error 0.23 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 30 min | 2.23 mmol/L | Standard Error 0.221 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 15 min | 0.828 mmol/L | Standard Error 0.142 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 90 minutes | 3.48 mmol/L | Standard Error 0.239 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 150 min at wk 20 | -0.830 mmol/L | Standard Error 0.286 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 90 min at wk 20 | -0.952 mmol/L | Standard Error 0.322 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 60 min at wk 20 | -0.720 mmol/L | Standard Error 0.329 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change fr baseline glucose at 15 min at wk 20 | 0.150 mmol/L | Standard Error 0.157 |
| Rosiglitazone | Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Baseline glucose at 120 minutes | 2.31 mmol/L | Standard Error 0.235 |
Secondary
Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT).
Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 180 min at wk 20 | 0.031 mmol/L | Standard Error 1.3 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 60 min | 27.92 mmol/L | Standard Error 4.68 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 150 min | 15.67 mmol/L | Standard Error 2.47 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 120 min | 19.56 mmol/L | Standard Error 2.99 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 60 min at wk 20 | -11.04 mmol/L | Standard Error 2.63 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 15 min at wk 20 | -1.71 mmol/L | Standard Error 1.45 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 90 min at wk 20 | -9.42 mmol/L | Standard Error 2.72 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 90 min | 26.06 mmol/L | Standard Error 4.1 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 150 min at wk 20 | -7.48 mmol/L | Standard Error 1.74 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 180 min | 10.58 mmol/L | Standard Error 1.73 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 30 min | 19.81 mmol/L | Standard Error 2.28 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 15 min | 9.97 mmol/L | Standard Error 1.71 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 120 min at wk 20 | -11.26 mmol/L | Standard Error 1.99 |
| Exenatide | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 30 min at wk 20 | -3.00 mmol/L | Standard Error 1.9 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 120 min at wk 20 | -8.69 mmol/L | Standard Error 2 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 180 min | 8.18 mmol/L | Standard Error 1.73 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 15 min | 8.09 mmol/L | Standard Error 1.71 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 15 min at wk 20 | -1.84 mmol/L | Standard Error 1.45 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 30 min | 14.79 mmol/L | Standard Error 2.25 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 30 min at wk 20 | -2.63 mmol/L | Standard Error 1.89 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 60 min | 27.67 mmol/L | Standard Error 4.61 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 60 min at wk 20 | -7.47 mmol/L | Standard Error 2.59 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 90 min | 21.85 mmol/L | Standard Error 4.1 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 90 min at wk 20 | -9.27 mmol/L | Standard Error 2.74 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 120 min | 17.52 mmol/L | Standard Error 2.99 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 150 min | 12.74 mmol/L | Standard Error 2.43 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 150 min at wk 20 | -8.13 mmol/L | Standard Error 1.73 |
| Exenatide Plus Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 180 min at wk 20 | -5.26 mmol/L | Standard Error 1.3 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 150 min at wk 20 | -5.57 mmol/L | Standard Error 1.78 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 120 min | 25.47 mmol/L | Standard Error 3.04 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 30 min | 18.83 mmol/L | Standard Error 2.35 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 15 min at wk 20 | -0.455 mmol/L | Standard Error 1.52 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 120 min at wk 20 | -6.43 mmol/L | Standard Error 2.04 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 15 min | 7.53 mmol/L | Standard Error 1.79 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 180 min | 10.74 mmol/L | Standard Error 1.79 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 150 min | 18.11 mmol/L | Standard Error 2.51 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 30 min at wk 20 | -1.04 mmol/L | Standard Error 1.96 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 90 min | 32.25 mmol/L | Standard Error 4.36 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 60 min at wk 20 | -7.42 mmol/L | Standard Error 2.67 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 180 min at wk 20 | -4.04 mmol/L | Standard Error 1.34 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change fr baseline insulin at 90 min at wk 20 | -6.19 mmol/L | Standard Error 2.92 |
| Rosiglitazone | Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Baseline insulin at 60 min | 32.09 mmol/L | Standard Error 4.75 |
Secondary
Change in Insulin AUC in the First Stage From Baseline to Endpoint.
Change in insulin AUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.
Time frame: Week 20
Population: All patients in full analysis set who participated in clamp tests and have both baseline and endpoint
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Baseline insulin AUC | 200.50 uIU-min/ml | Standard Error 50.4 |
| Exenatide | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Change from baseline insulin AUC at week 20 | 134.88 uIU-min/ml | Standard Error 31.71 |
| Exenatide Plus Rosiglitazone | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Baseline insulin AUC | 136.84 uIU-min/ml | Standard Error 50.4 |
| Exenatide Plus Rosiglitazone | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Change from baseline insulin AUC at week 20 | 32.12 uIU-min/ml | Standard Error 31.65 |
| Rosiglitazone | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Baseline insulin AUC | 157.49 uIU-min/ml | Standard Error 53.66 |
| Rosiglitazone | Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Change from baseline insulin AUC at week 20 | -50.81 uIU-min/ml | Standard Error 33.59 |
p-value: 0.079ANCOVA
Secondary
Change in Insulin iAUC From Baseline to Endpoint.
Change in insulin iAUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.
Time frame: Week 20
Population: All patients in full analysis set who participated in clamp tests and have both baseline and endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Insulin iAUC From Baseline to Endpoint. | Baseline insulin iAUC | 5.98 uIU-min/ml | Standard Error 14.29 |
| Exenatide | Change in Insulin iAUC From Baseline to Endpoint. | Change from baseline insulin iAUC at week 20 | 99.08 uIU-min/ml | Standard Error 24.23 |
| Exenatide Plus Rosiglitazone | Change in Insulin iAUC From Baseline to Endpoint. | Baseline insulin iAUC | -9.92 uIU-min/ml | Standard Error 14.29 |
| Exenatide Plus Rosiglitazone | Change in Insulin iAUC From Baseline to Endpoint. | Change from baseline insulin iAUC at week 20 | 53.71 uIU-min/ml | Standard Error 24.54 |
| Rosiglitazone | Change in Insulin iAUC From Baseline to Endpoint. | Baseline insulin iAUC | 23.09 uIU-min/ml | Standard Error 15.21 |
| Rosiglitazone | Change in Insulin iAUC From Baseline to Endpoint. | Change from baseline insulin iAUC at week 20 | 11.51 uIU-min/ml | Standard Error 26.15 |
p-value: 0.252ANCOVA
Secondary
Change in Insulin Sensitivity Index as Measured by M-value.
Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20.
Time frame: Week 20
Population: All patients in full analysis set who participated in clamp test and have both baseline and endpoint measurements.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Insulin Sensitivity Index as Measured by M-value. | M-Value at baseline | 3.89 mg/kg-min | Standard Error 0.495 |
| Exenatide | Change in Insulin Sensitivity Index as Measured by M-value. | Change in M-Value from baseline at week 20 | 0.477 mg/kg-min | Standard Error 0.425 |
| Exenatide Plus Rosiglitazone | Change in Insulin Sensitivity Index as Measured by M-value. | Change in M-Value from baseline at week 20 | 2.07 mg/kg-min | Standard Error 0.44 |
| Exenatide Plus Rosiglitazone | Change in Insulin Sensitivity Index as Measured by M-value. | M-Value at baseline | 2.49 mg/kg-min | Standard Error 0.495 |
| Rosiglitazone | Change in Insulin Sensitivity Index as Measured by M-value. | M-Value at baseline | 4.02 mg/kg-min | Standard Error 0.511 |
| Rosiglitazone | Change in Insulin Sensitivity Index as Measured by M-value. | Change in M-Value from baseline at week 20 | 1.42 mg/kg-min | Standard Error 0.442 |
p-value: 0.308ANCOVA
Secondary
Change in Lean Body Mass During a Meal Challenge Test (MCT)
Change in lean body mass from baseline to week 20, as assessed during an MCT
Time frame: 20 weeks
Population: All Patients in Full Analysis Set Who Have Both Baseline and Endpoint Measurements
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Baseline lean body mass | 64.62 kg | Standard Error 2.11 |
| Exenatide | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Change in lean body mass at week 20 | -2.99 kg | Standard Error 1.39 |
| Exenatide Plus Rosiglitazone | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Baseline lean body mass | 60.94 kg | Standard Error 2.08 |
| Exenatide Plus Rosiglitazone | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Change in lean body mass at week 20 | 0.532 kg | Standard Error 1.37 |
| Rosiglitazone | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Baseline lean body mass | 61.09 kg | Standard Error 2.14 |
| Rosiglitazone | Change in Lean Body Mass During a Meal Challenge Test (MCT) | Change in lean body mass at week 20 | 1.23 kg | Standard Error 1.41 |
p-value: 0.724ANCOVA
Secondary
Change in Percent Body Fat During a Meal Challenge Test (MCT)
Change in percent body fat from baseline to week 20, as assessed during an MCT
Time frame: 20 weeks
Population: All Patients in Full Analysis Set Who Have Both Baseline and Endpoint Measurement
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Change in percent body fat at week 20 | -1.40 percentage | Standard Error 1.06 |
| Exenatide | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Baseline percent body fat | 33.42 percentage | Standard Error 1.16 |
| Exenatide Plus Rosiglitazone | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Change in percent body fat at week 20 | -0.347 percentage | Standard Error 1.04 |
| Exenatide Plus Rosiglitazone | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Baseline percent body fat | 34.07 percentage | Standard Error 1.15 |
| Rosiglitazone | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Baseline percent body fat | 32.50 percentage | Standard Error 1.18 |
| Rosiglitazone | Change in Percent Body Fat During a Meal Challenge Test (MCT) | Change in percent body fat at week 20 | -1.18 percentage | Standard Error 1.08 |
p-value: 0.581ANCOVA
Secondary
Change in Waist Circumference
Change in waist circumference from baseline to week 20
Time frame: 20 weeks
Population: All Patients Who Have Both Baseline and At Least One Post Baseline Value in Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Waist Circumference | Baseline waist circumference | 105.98 cm | Standard Error 1.68 |
| Exenatide | Change in Waist Circumference | Change in waist circumference at Week 20 | -2.95 cm | Standard Error 0.975 |
| Exenatide Plus Rosiglitazone | Change in Waist Circumference | Baseline waist circumference | 106.85 cm | Standard Error 1.67 |
| Exenatide Plus Rosiglitazone | Change in Waist Circumference | Change in waist circumference at Week 20 | -2.38 cm | Standard Error 0.955 |
| Rosiglitazone | Change in Waist Circumference | Baseline waist circumference | 105.34 cm | Standard Error 1.67 |
| Rosiglitazone | Change in Waist Circumference | Change in waist circumference at Week 20 | -0.225 cm | Standard Error 0.969 |
p-value: 0.117MMRM
Secondary
Change in Waist-to-hip Ratio
Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20
Time frame: 20 weeks
Population: All Patients Who Have Both Baseline and At Least One Post Baseline Value in Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Waist-to-hip Ratio | Baseline waist-to-hip ratio | 0.939 ratio (cm/cm) | Standard Error 0.012 |
| Exenatide | Change in Waist-to-hip Ratio | Change in waist-to-hip ratio at week 20 | -0.016 ratio (cm/cm) | Standard Error 0.011 |
| Exenatide Plus Rosiglitazone | Change in Waist-to-hip Ratio | Baseline waist-to-hip ratio | 0.957 ratio (cm/cm) | Standard Error 0.012 |
| Exenatide Plus Rosiglitazone | Change in Waist-to-hip Ratio | Change in waist-to-hip ratio at week 20 | -0.022 ratio (cm/cm) | Standard Error 0.01 |
| Rosiglitazone | Change in Waist-to-hip Ratio | Baseline waist-to-hip ratio | 0.943 ratio (cm/cm) | Standard Error 0.012 |
| Rosiglitazone | Change in Waist-to-hip Ratio | Change in waist-to-hip ratio at week 20 | -0.016 ratio (cm/cm) | Standard Error 0.011 |
p-value: 0.71MMRM
Secondary
Hypoglycemia Rate Per 30 Days Per Patient
Average number of episodes of hypoglycemia per 30 days per patient
Time frame: 20 weeks
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Hypoglycemia Rate Per 30 Days Per Patient | 0.391 hypoglycemia events / 30 days / patient | Standard Deviation 0.298 |
| Exenatide Plus Rosiglitazone | Hypoglycemia Rate Per 30 Days Per Patient | 0.594 hypoglycemia events / 30 days / patient | Standard Deviation 0.436 |
| Rosiglitazone | Hypoglycemia Rate Per 30 Days Per Patient | 0.853 hypoglycemia events / 30 days / patient | Standard Deviation 1.05 |
p-value: 0.436ANOVA
Secondary
Incidence of Hypoglycemia Events
Number of subjects experiencing hypoglycemia at any point during the study
Time frame: 20 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Incidence of Hypoglycemia Events | 8 participants |
| Exenatide Plus Rosiglitazone | Incidence of Hypoglycemia Events | 9 participants |
| Rosiglitazone | Incidence of Hypoglycemia Events | 6 participants |
p-value: 0.575Fisher Exact
Secondary
Pedal Edema Score
Pedal edema scores experienced by each patient throughout the study (1+ indicates a patient experienced a pedal edema score of 1 , 2, or 3; 2+ indicates a patient experienced a pedal edema score of 2 or 3, etc.) Scale: 1. Slight pitting, no visible distortion, disappears rapidly 2. A somewhat deeper pit than in 1+, but again no readily detectable distortion, and it disappears in 10 - 15 seconds 3. The pit is noticeably deep and may last more than a minute; the dependent extremity looks fuller and swollen 4. The pit is very deep, lasts as long as 2 - 5 minutes, and the dependent extremity is grossly distorted
Time frame: 20 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exenatide | Pedal Edema Score | No edema | 37 participants |
| Exenatide | Pedal Edema Score | Edema score: 1+ | 7 participants |
| Exenatide | Pedal Edema Score | Edema score: 2+ | 1 participants |
| Exenatide | Pedal Edema Score | Edema score: 3+ | 0 participants |
| Exenatide Plus Rosiglitazone | Pedal Edema Score | Edema score: 3+ | 0 participants |
| Exenatide Plus Rosiglitazone | Pedal Edema Score | No edema | 34 participants |
| Exenatide Plus Rosiglitazone | Pedal Edema Score | Edema score: 2+ | 3 participants |
| Exenatide Plus Rosiglitazone | Pedal Edema Score | Edema score: 1+ | 11 participants |
| Rosiglitazone | Pedal Edema Score | Edema score: 3+ | 1 participants |
| Rosiglitazone | Pedal Edema Score | Edema score: 1+ | 14 participants |
| Rosiglitazone | Pedal Edema Score | Edema score: 2+ | 6 participants |
| Rosiglitazone | Pedal Edema Score | No edema | 30 participants |
p-value: 0.168Generalized Linear Model
Secondary
Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT).
Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT.
Time frame: Week 20
Population: All patients in full analysis set who have both baseline and endpoint measurement.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Baseline AUC for insulin during MCT | 5171.40 uIU-min/ml | Standard Error 522.82 |
| Exenatide | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of insulin AUC during MCT | 0.806 uIU-min/ml | Standard Error 0.063 |
| Exenatide Plus Rosiglitazone | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Baseline AUC for insulin during MCT | 4324.13 uIU-min/ml | Standard Error 430.87 |
| Exenatide Plus Rosiglitazone | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of insulin AUC during MCT | 0.664 uIU-min/ml | Standard Error 0.052 |
| Rosiglitazone | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Baseline AUC for insulin during MCT | 5816.83 uIU-min/ml | Standard Error 596.91 |
| Rosiglitazone | Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Ratio(endpoint/baseline) of insulin AUC during MCT | 0.722 uIU-min/ml | Standard Error 0.058 |
p-value: 0.465ANCOVA