Type 2 Diabetes
Conditions
Keywords
diabetes, exenatide, insulin glargine, Lilly, Amylin
Brief summary
This is a phase 3 trial designed to compare the effects of twice daily exenatide plus oral antidiabetic agents (OADs) and once-daily insulin glargine plus OADs with respect to glycemic control, as measured by hemoglobin A1c, with minimum weight gain, in patients with uncontrolled type 2 diabetes on OADs.
Interventions
DRUGexenatide
subcutaneous injection, 5mcg or 10mcg, twice a day
DRUGinsulin glargine
subcutaneous injection, titrated to target blood glucose level, once 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
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes * Currently being treated with the following: Dual or triple oral therapy - on a stable combination and dose for at least 3 months. * HbA1c between 7.5% and 10.0%. * BMI \>27.
Exclusion criteria
* Receive chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to study. * Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which a medical or surgical treatment was given) within 30 days prior to entry into the study. * Treatment with the following medications: \*Insulin as outpatient therapy within last 3 months; \*Meglitinides, or acarbose within the last 3 months; \*Regular use of any drugs that directly affect gastrointestinal motility; \*Any previous (study) therapy with exenatide or glucagon-like peptide-1 (GLP-1) analogue; \*Anti-obesity agent use within the last 3 months. * Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Who Achieved HbA1c ≤ 7.4% With Minimal Weight Gain (≤ 1kg) | 26 weeks | Composite endpoint evaluating effect of treatment on glycemic control and weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Serum Glucose | 26 weeks | Change in fasting serum glucose from baseline (week 0) to endpoint (week 26) |
| Percent of Patients Achieving HbA1c ≤ 7.4% | 26 weeks | Percent of patients achieving specified HbA1c target at endpoint |
| Percent of Patients Achieving HbA1c < 7% | 26 weeks | Percent of patients achieving specified HbA1c target at endpoint |
| Percent of Patients Achieving HbA1c < 6.5% | 26 weeks | Percent of patients achieving specified HbA1c target at endpoint |
| Change in 7 Point Self Monitored Blood Glucose Profile | 26 weeks | Change from baseline to endpoint in self monitored blood glucose levels measured at 7 time points during the day |
| Change in Body Mass Index (BMI) | 26 weeks | Change in BMI from baseline to endpoint |
| Change in Waist Circumference | 26 Weeks | Change in waist circumference from baseline to endpoint |
| Change in Waist-to-hip Ratio | 26 weeks | Change in waist-to-hip ratio from baseline to endpoint |
| Change in Body Weight | 26 weeks | Change in body weight from baseline to endpoint |
| Percent Change in Body Weight | 26 Weeks | Percent change in baseline body weight at endpoint |
| Percent of Patients Achieving 5% Weight Loss | 26 weeks | Percent of patients who lost at least 5% of baseline body weight at endpoint |
| Percent of Patients Achieving 10% Weight Loss | 26 weeks | Percent of patients who lost at least 10% of baseline body weight at endpoint |
| Change in Systolic Blood Pressure | 26 weeks | Change in systolic blood pressure from baseline to endpoint |
| Percent of Patients Who Achieved HbA1c ≤ 7.4% and Weight Gain ≤ 0.5kg | 26 weeks | Composite endpoint evaluating effect of treatment on glycemic control and weight |
| Change in Fasting Serum Total Cholesterol (TC) | 26 weeks | Change in TC from baseline to endpoint |
| Change in High Density Lipoprotein (HDL) Cholesterol | 26 weeks | Change in HDL cholesterol from baseline to endpoint |
| Change in TC to HDL Cholesterol Ratio | 26 weeks | Change in TC to HDL cholesterol ratio from baseline to endpoint |
| Change in Fasting Serum Triglycerides | 26 weeks | Change in fasting serum triglycerides from baseline to endpoint |
| Change in Low Density Lipoprotein (LDL) Cholesterol | 26 weeks | Change in LDL cholesterol from baseline to endpoint |
| Change in Apolipoprotein-B | 26 weeks | Change in apolipoprotein-B from baseline to endpoint |
| Incidence of Hypoglycemic Episodes | 26 weeks | Percent of total patients in each arm experiencing hypoglycemia at any point in the 26 week study |
| Incidence of Nocturnal Hypoglycemic Episodes | 26 weeks | Percent of total patients in each arm experiencing nocturnal hypoglycemia at any point in the 26 week study |
| Incidence of Severe Hypoglycemic Episodes | 26 weeks | Percent of total patients in each arm experiencing severe hypoglycemia at any point during the 26 week study |
| Hypoglycemic Rate Per 30 Days | 26 weeks | Number of hypoglycemic episodes per patient adjusted per 30 days |
| Nocturnal Hypoglycemic Rate Per 30 Days | 26 weeks | Number of nocturnal hypoglycemic episodes per patient adjusted per 30 days |
| Severe Hypoglycemic Rate Per 30 Days | 26 weeks | Number of severe hypoglycemic episodes per patient adjusted per 30 days |
| Change in Diastolic Blood Pressure | 26 weeks | Change in diastolic blood pressure from baseline to endpoint |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted at 35 study centers in the United Kingdom. Recruitment occurred from June 2006 to October 2007.
Pre-assignment details
One patient assigned to the Insulin Glargine group withdrew from the study prior to receiving study drug. This patient is not included in the analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide 5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks | 118 |
| Insulin Glargine dosing based on treat to target protocol | 116 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 |
| Overall Study | Entry criterion not met | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Subject decision | 8 | 2 |
Baseline characteristics
| Characteristic | Exenatide | Insulin Glargine | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 10.2 | 56.2 years STANDARD_DEVIATION 7.9 | 56.5 years STANDARD_DEVIATION 9.1 |
| Baseline apolipoprotein-B | 0.84 g/L STANDARD_DEVIATION 0.24 | 0.88 g/L STANDARD_DEVIATION 0.24 | 0.86 g/L STANDARD_DEVIATION 0.24 |
| Baseline fasting serum glucose | 10.84 mmol/L STANDARD_DEVIATION 2.23 | 10.12 mmol/L STANDARD_DEVIATION 2.22 | 10.48 mmol/L STANDARD_DEVIATION 2.25 |
| Baseline fasting serum total cholesterol (TC) | 4.45 mmol/L STANDARD_DEVIATION 1.05 | 4.63 mmol/L STANDARD_DEVIATION 1.2 | 4.54 mmol/L STANDARD_DEVIATION 1.13 |
| Baseline fasting serum triglycerides | 1.94 mmol/L STANDARD_DEVIATION 1.01 | 2.31 mmol/L STANDARD_DEVIATION 2.24 | 2.13 mmol/L STANDARD_DEVIATION 1.75 |
| Baseline high density lipoprotein (HDL) cholesterol | 1.14 mmol/L STANDARD_DEVIATION 0.24 | 1.15 mmol/L STANDARD_DEVIATION 0.29 | 1.15 mmol/L STANDARD_DEVIATION 0.27 |
| Baseline low density lipoprotein (LDL) cholesterol | 2.38 mmol/L STANDARD_DEVIATION 0.82 | 2.49 mmol/L STANDARD_DEVIATION 1.02 | 2.43 mmol/L STANDARD_DEVIATION 0.93 |
| Baseline total cholesterol to high density lipoprotein cholesterol ratio | 4.00 ratio STANDARD_DEVIATION 1.1 | 4.29 ratio STANDARD_DEVIATION 2.15 | 4.15 ratio STANDARD_DEVIATION 1.72 |
| Region of Enrollment United Kingdom | 118 participants | 116 participants | 234 participants |
| Sex: Female, Male Female | 35 Participants | 39 Participants | 74 Participants |
| Sex: Female, Male Male | 83 Participants | 77 Participants | 160 Participants |
| Types of oral antidiabetic medication combinations administered at baseline metformin and sulfonylurea | 50 participants | 49 participants | 99 participants |
| Types of oral antidiabetic medication combinations administered at baseline metformin and thiazolidinedione | 17 participants | 15 participants | 32 participants |
| Types of oral antidiabetic medication combinations administered at baseline metformin, sulfonylurea, and thiazolidinedione | 48 participants | 47 participants | 95 participants |
| Types of oral antidiabetic medication combinations administered at baseline other | 1 participants | 1 participants | 2 participants |
| Types of oral antidiabetic medication combinations administered at baseline sulfonylurea and thiazolidinedione | 2 participants | 4 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 105 / — | 94 / — |
| serious Total, serious adverse events | 5 / — | 5 / — |
Outcome results
Primary
Percent of Patients Who Achieved HbA1c ≤ 7.4% With Minimal Weight Gain (≤ 1kg)
Composite endpoint evaluating effect of treatment on glycemic control and weight
Time frame: 26 weeks
Population: Full Analysis Set; The last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value. Patients who did not have a baseline weight measurement and/or missing post-baseline measurements for HbA1c and/or weight were included in the analysis as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Who Achieved HbA1c ≤ 7.4% With Minimal Weight Gain (≤ 1kg) | 53.4 percentage of participants |
| Insulin Glargine | Percent of Patients Who Achieved HbA1c ≤ 7.4% With Minimal Weight Gain (≤ 1kg) | 19.8 percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the primary outcome divided by the odds of a patient in the insulin glargine arm achieving the primary outcomep-value: <0.00195% CI: [2.62, 8.46]Regression, Logistic
Secondary
Change in 7 Point Self Monitored Blood Glucose Profile
Change from baseline to endpoint in self monitored blood glucose levels measured at 7 time points during the day
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-breakfast: Baseline (Week 0) | 9.98 mmol/L | Standard Deviation 2.11 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-breakfast: Change at endpoint (Week 26) | -2.01 mmol/L | Standard Deviation 2.14 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after breakfast: Baseline (Week 0) | 13.53 mmol/L | Standard Deviation 3.07 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after breakfast: Change at endpt (Week 26) | -5.09 mmol/L | Standard Deviation 3.52 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-lunch: Baseline (Week 0) | 9.95 mmol/L | Standard Deviation 3.24 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-lunch: Change at endpoint (Week 26) | -2.21 mmol/L | Standard Deviation 3.11 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after lunch: Baseline (Week 0) | 12.07 mmol/L | Standard Deviation 3.27 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after lunch: Change at endpoint (Week 26) | -3.20 mmol/L | Standard Deviation 3.3 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-dinner: Baseline (Week 0) | 9.95 mmol/L | Standard Deviation 2.97 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-dinner: Change at endpoint (Week 26) | -2.13 mmol/L | Standard Deviation 2.89 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after dinner: Baseline (Week 0) | 12.59 mmol/L | Standard Deviation 3.28 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after dinner: Change at endpoint (Week 26) | -4.59 mmol/L | Standard Deviation 3.3 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Bedtime: Baseline (Week 0) | 11.63 mmol/L | Standard Deviation 3.23 |
| Exenatide | Change in 7 Point Self Monitored Blood Glucose Profile | Bedtime: Change at endpoint (Week 26) | -3.56 mmol/L | Standard Deviation 3.19 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after dinner: Baseline (Week 0) | 11.80 mmol/L | Standard Deviation 2.62 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-breakfast: Baseline (Week 0) | 9.88 mmol/L | Standard Deviation 2.07 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after lunch: Change at endpoint (Week 26) | -2.48 mmol/L | Standard Deviation 3.17 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-breakfast: Change at endpoint (Week 26) | -3.99 mmol/L | Standard Deviation 2.39 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Bedtime: Baseline (Week 0) | 11.24 mmol/L | Standard Deviation 3.05 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after breakfast: Baseline (Week 0) | 13.33 mmol/L | Standard Deviation 2.87 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-dinner: Baseline (Week 0) | 9.37 mmol/L | Standard Deviation 2.73 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after breakfast: Change at endpt (Week 26) | -3.95 mmol/L | Standard Deviation 3.89 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after dinner: Change at endpoint (Week 26) | -2.06 mmol/L | Standard Deviation 3.22 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-lunch: Baseline (Week 0) | 9.54 mmol/L | Standard Deviation 2.71 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-dinner: Change at endpoint (Week 26) | -1.46 mmol/L | Standard Deviation 4.76 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Pre-lunch: Change at endpoint (Week 26) | -2.59 mmol/L | Standard Deviation 3.27 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | Bedtime: Change at endpoint (Week 26) | -2.20 mmol/L | Standard Deviation 3.47 |
| Insulin Glargine | Change in 7 Point Self Monitored Blood Glucose Profile | 2 hrs after lunch: Baseline (Week 0) | 11.15 mmol/L | Standard Deviation 2.59 |
Secondary
Change in Apolipoprotein-B
Change in apolipoprotein-B from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Apolipoprotein-B | -0.09 g/L | Standard Error 0.02 |
| Insulin Glargine | Change in Apolipoprotein-B | -0.08 g/L | Standard Error 0.02 |
p-value: 0.667ANCOVA
Secondary
Change in Body Mass Index (BMI)
Change in BMI from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Body Mass Index (BMI) | Baseline (Week 0) | 34.49 kg/m^2 | Standard Error 0.49 |
| Exenatide | Change in Body Mass Index (BMI) | Change at endpoint (Week 26) | -0.95 kg/m^2 | Standard Error 0.11 |
| Insulin Glargine | Change in Body Mass Index (BMI) | Baseline (Week 0) | 33.71 kg/m^2 | Standard Error 0.49 |
| Insulin Glargine | Change in Body Mass Index (BMI) | Change at endpoint (Week 26) | 1.01 kg/m^2 | Standard Error 0.11 |
p-value: <0.001Mixed Model Repeated Measures
Secondary
Change in Body Weight
Change in body weight from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Body Weight | Baseline (Week 0) | 101.19 kg | Standard Error 1.68 |
| Exenatide | Change in Body Weight | Change at endpoint (Week 26) | -2.73 kg | Standard Error 0.31 |
| Insulin Glargine | Change in Body Weight | Baseline (Week 0) | 97.93 kg | Standard Error 1.7 |
| Insulin Glargine | Change in Body Weight | Change at endpoint (Week 26) | 2.98 kg | Standard Error 0.31 |
p-value: <0.001Mixed Model Repeated Measures
Secondary
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Diastolic Blood Pressure | Baseline (Week 0) | 79.6 mmHg | Standard Error 0.8 |
| Exenatide | Change in Diastolic Blood Pressure | Change at endpoint (Week 26) | -0.8 mmHg | Standard Error 0.7 |
| Insulin Glargine | Change in Diastolic Blood Pressure | Baseline (Week 0) | 79.7 mmHg | Standard Error 0.8 |
| Insulin Glargine | Change in Diastolic Blood Pressure | Change at endpoint (Week 26) | 0.9 mmHg | Standard Error 0.7 |
p-value: 0.1Mixed Model Repeated Measures
Secondary
Change in Fasting Serum Glucose
Change in fasting serum glucose from baseline (week 0) to endpoint (week 26)
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Fasting Serum Glucose | -2.12 mmol/L | Standard Error 0.25 |
| Insulin Glargine | Change in Fasting Serum Glucose | -3.61 mmol/L | Standard Error 0.25 |
p-value: <0.001ANCOVA
Secondary
Change in Fasting Serum Total Cholesterol (TC)
Change in TC from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Fasting Serum Total Cholesterol (TC) | -0.36 mmol/L | Standard Error 0.07 |
| Insulin Glargine | Change in Fasting Serum Total Cholesterol (TC) | -0.21 mmol/L | Standard Error 0.07 |
p-value: 0.125ANCOVA
Secondary
Change in Fasting Serum Triglycerides
Change in fasting serum triglycerides from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Fasting Serum Triglycerides | -0.33 mmol/L | Standard Error 0.08 |
| Insulin Glargine | Change in Fasting Serum Triglycerides | -0.38 mmol/L | Standard Error 0.08 |
p-value: 0.65ANCOVA
Secondary
Change in High Density Lipoprotein (HDL) Cholesterol
Change in HDL cholesterol from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in High Density Lipoprotein (HDL) Cholesterol | 0.01 mmol/L | Standard Error 0.01 |
| Insulin Glargine | Change in High Density Lipoprotein (HDL) Cholesterol | 0.02 mmol/L | Standard Error 0.01 |
p-value: 0.471ANCOVA
Secondary
Change in Low Density Lipoprotein (LDL) Cholesterol
Change in LDL cholesterol from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in Low Density Lipoprotein (LDL) Cholesterol | -0.25 mmol/L | Standard Error 0.06 |
| Insulin Glargine | Change in Low Density Lipoprotein (LDL) Cholesterol | -0.07 mmol/L | Standard Error 0.05 |
p-value: 0.017ANCOVA
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Systolic Blood Pressure | Baseline (Week 0) | 134.0 mmHg | Standard Error 1.5 |
| Exenatide | Change in Systolic Blood Pressure | Change at endpoint (Week 26) | -3.6 mmHg | Standard Error 1.2 |
| Insulin Glargine | Change in Systolic Blood Pressure | Baseline (Week 0) | 134.7 mmHg | Standard Error 1.5 |
| Insulin Glargine | Change in Systolic Blood Pressure | Change at endpoint (Week 26) | 0.6 mmHg | Standard Error 1.2 |
p-value: 0.014Mixed Model Repeated Measures
Secondary
Change in TC to HDL Cholesterol Ratio
Change in TC to HDL cholesterol ratio from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Change in TC to HDL Cholesterol Ratio | -0.40 Ratio | Standard Error 0.1 |
| Insulin Glargine | Change in TC to HDL Cholesterol Ratio | -0.34 Ratio | Standard Error 0.09 |
p-value: 0.601ANCOVA
Secondary
Change in Waist Circumference
Change in waist circumference from baseline to endpoint
Time frame: 26 Weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Waist Circumference | Baseline (Week 0) | 112.07 cm | Standard Error 1.3 |
| Exenatide | Change in Waist Circumference | Change at endpoint (Week 26) | -2.19 cm | Standard Error 0.54 |
| Insulin Glargine | Change in Waist Circumference | Baseline (Week 0) | 110.64 cm | Standard Error 1.32 |
| Insulin Glargine | Change in Waist Circumference | Change at endpoint (Week 26) | 1.97 cm | Standard Error 0.54 |
p-value: <0.001Mixed Model Repeated Measures
Secondary
Change in Waist-to-hip Ratio
Change in waist-to-hip ratio from baseline to endpoint
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide | Change in Waist-to-hip Ratio | Baseline (Week 0) | 0.99 Ratio | Standard Error 0.01 |
| Exenatide | Change in Waist-to-hip Ratio | Change at endpoint (Week 26) | -0.02 Ratio | Standard Error 0 |
| Insulin Glargine | Change in Waist-to-hip Ratio | Baseline (Week 0) | 0.98 Ratio | Standard Error 0.01 |
| Insulin Glargine | Change in Waist-to-hip Ratio | Change at endpoint (Week 26) | 0.01 Ratio | Standard Error 0 |
p-value: <0.001Mixed Model Repeated Measures
Secondary
Hypoglycemic Rate Per 30 Days
Number of hypoglycemic episodes per patient adjusted per 30 days
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Hypoglycemic Rate Per 30 Days | 0.069 Number of episodes per 30 days |
| Insulin Glargine | Hypoglycemic Rate Per 30 Days | 0.164 Number of episodes per 30 days |
p-value: 0.113ANCOVA on ranks
Secondary
Incidence of Hypoglycemic Episodes
Percent of total patients in each arm experiencing hypoglycemia at any point in the 26 week study
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Incidence of Hypoglycemic Episodes | 50.0 percent |
| Insulin Glargine | Incidence of Hypoglycemic Episodes | 59.6 percent |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.13995% CI: [0.401, 1.136]Regression, Logistic
Secondary
Incidence of Nocturnal Hypoglycemic Episodes
Percent of total patients in each arm experiencing nocturnal hypoglycemia at any point in the 26 week study
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Incidence of Nocturnal Hypoglycemic Episodes | 11.9 percent |
| Insulin Glargine | Incidence of Nocturnal Hypoglycemic Episodes | 29.8 percent |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.00195% CI: [0.159, 0.63]Regression, Logistic
Secondary
Incidence of Severe Hypoglycemic Episodes
Percent of total patients in each arm experiencing severe hypoglycemia at any point during the 26 week study
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Incidence of Severe Hypoglycemic Episodes | 4.2 percent |
| Insulin Glargine | Incidence of Severe Hypoglycemic Episodes | 5.3 percent |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.71695% CI: [0.235, 2.705]Regression, Logistic
Secondary
Nocturnal Hypoglycemic Rate Per 30 Days
Number of nocturnal hypoglycemic episodes per patient adjusted per 30 days
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Nocturnal Hypoglycemic Rate Per 30 Days | 0.000 Number of episodes per 30 days |
| Insulin Glargine | Nocturnal Hypoglycemic Rate Per 30 Days | 0.000 Number of episodes per 30 days |
p-value: <0.001ANCOVA on ranks
Secondary
Percent Change in Body Weight
Percent change in baseline body weight at endpoint
Time frame: 26 Weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Percent Change in Body Weight | -2.8 Percentage | Standard Error 0.3 |
| Insulin Glargine | Percent Change in Body Weight | 3.1 Percentage | Standard Error 0.3 |
p-value: <0.001Mixed Models Repeated Measures
Secondary
Percent of Patients Achieving 10% Weight Loss
Percent of patients who lost at least 10% of baseline body weight at endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward. For change in weight, patients should have a baseline and at least one post-baseline weight measurement. Otherwise, these patients are included as non-responders in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Achieving 10% Weight Loss | 4.2 Percentage of participants |
| Insulin Glargine | Percent of Patients Achieving 10% Weight Loss | 0.0 Percentage of participants |
Secondary
Percent of Patients Achieving 5% Weight Loss
Percent of patients who lost at least 5% of baseline body weight at endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward. For change in weight, patients should have a baseline and at least one post-baseline weight measurement. Otherwise, these patients are included as non-responders in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Achieving 5% Weight Loss | 19.5 Percentage of participants |
| Insulin Glargine | Percent of Patients Achieving 5% Weight Loss | 0.9 Percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.00195% CI: [3.7, 210.54]Regression, Logistic
Secondary
Percent of Patients Achieving HbA1c < 6.5%
Percent of patients achieving specified HbA1c target at endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Achieving HbA1c < 6.5% | 15.3 Percentage of participants |
| Insulin Glargine | Percent of Patients Achieving HbA1c < 6.5% | 11.2 Percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.36395% CI: [0.66, 3.07]Regression, Logistic
Secondary
Percent of Patients Achieving HbA1c < 7%
Percent of patients achieving specified HbA1c target at endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Achieving HbA1c < 7% | 34.7 Percentage of participants |
| Insulin Glargine | Percent of Patients Achieving HbA1c < 7% | 43.1 Percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.19195% CI: [0.42, 1.19]Regression, Logistic
Secondary
Percent of Patients Achieving HbA1c ≤ 7.4%
Percent of patients achieving specified HbA1c target at endpoint
Time frame: 26 weeks
Population: Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Achieving HbA1c ≤ 7.4% | 54.2 Percentage of participants |
| Insulin Glargine | Percent of Patients Achieving HbA1c ≤ 7.4% | 61.2 Percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: 0.2895% CI: [0.44, 1.26]Regression, Logistic
Secondary
Percent of Patients Who Achieved HbA1c ≤ 7.4% and Weight Gain ≤ 0.5kg
Composite endpoint evaluating effect of treatment on glycemic control and weight
Time frame: 26 weeks
Population: Full Analysis Set; The last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value. Patients who did not have a baseline weight measurement and/or missing post-baseline measurements for HbA1c and/or weight were included in the analysis as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide | Percent of Patients Who Achieved HbA1c ≤ 7.4% and Weight Gain ≤ 0.5kg | 52.5 Percentage of participants |
| Insulin Glargine | Percent of Patients Who Achieved HbA1c ≤ 7.4% and Weight Gain ≤ 0.5kg | 16.4 Percentage of participants |
Comparison: Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcomep-value: <0.00195% CI: [3.11, 10.64]Regression, Logistic
Secondary
Severe Hypoglycemic Rate Per 30 Days
Number of severe hypoglycemic episodes per patient adjusted per 30 days
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exenatide | Severe Hypoglycemic Rate Per 30 Days | 0.000 Number of episodes per 30 days |
| Insulin Glargine | Severe Hypoglycemic Rate Per 30 Days | 0.000 Number of episodes per 30 days |
p-value: 0.74ANCOVA on ranks