Effect of Exenatide Plus Metformin vs. Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Type 2 Diabetes

This study has been completed.

Sponsor:

Collaborator:

Eli Lilly and Company

Information provided by (Responsible Party):

Amylin Pharmaceuticals, LLC.

ClinicalTrials.gov Identifier:

NCT00434954

First received: February 12, 2007

Last updated: February 11, 2013

Last verified: February 2013

History of Changes

Results First Received: June 25, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Type 2 Diabetes Mellitus
Interventions:	Drug: exenatide twice daily (BID) Drug: premixed insulin aspart twice daily (BID)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients treated with metformin (MET only;confirmatory population used for primary analysis) and additional patients treated with metformin plus either sulfonylurea or meglitinide (MET+SU; exploratory population) were enrolled at a 3:1 ratio; metformin was continued.Within each population, patients were then randomly assigned 1:1 to study treatment

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Participant Flow: Overall Study

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
STARTED	248	246
Started - Previous Treatment MET Only	182	181
Started - Previous Treatment MET + SU	66	65
Full Analysis Set (FAS) Overall	247 ^[1]	233 ^[1]
FAS - Previous Treatment MET Only	181 ^[2]	173 ^[2]
FAS - Previous Treatment MET + SU	66	60
Completed - Previous Treatment MET Only	135	137
Completed - Previous Treatment MET + SU	31	38
COMPLETED	166	175
NOT COMPLETED	82	71
Adverse Event	17	2
Entry criteria not met	14	16
Lost to Follow-up	0	1
Physician Decision	6	3
Protocol Violation	36	27
Sponsor decision	1	0
Subject decision	8	22

[1]	FAS=received >=1 dose of study drug. Adverse event data reported for Overall FAS.
[2]	Baseline and efficacy data reported for "FAS-Previous Treatment MET Only" group.

Baseline Characteristics

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Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks
Total	Total of all reporting groups

Baseline Measures

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily	Total
Number of Participants [units: participants]	181	173	354
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	138	133	271
>=65 years	43	40	83
Age [units: years] Mean ± Standard Deviation	57.2 ± 10.03	56.9 ± 9.94	57.1 ± 9.97
Gender [units: participants]
Female	73	77	150
Male	108	96	204
Body Mass Index (BMI) [units: kg / m^2] Mean ± Standard Deviation	33.4 ± 4.23	32.9 ± 4.37	33.2 ± 4.30
Body Weight [units: kg] Mean ± Standard Deviation	99.4 ± 16.22	96.6 ± 17.40	98.0 ± 16.85
Duration of Diabetes [units: years] Mean ± Standard Deviation	4.8 ± 4.39	5.2 ± 4.67	5.0 ± 4.53
Glycosylated hemoglobin (HbA1c) [units: percentage] Mean ± Standard Deviation	7.89 ± 0.822	7.88 ± 0.918	7.88 ± 0.869

Outcome Measures

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1. Primary:

Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline and 26 weeks ]

Measure Type	Primary
Measure Title	Change in Glycosylated Hemoglobin (HbA1c)
Measure Description	Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS) and had baseline and at least one post-baseline value available

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Change in Glycosylated Hemoglobin (HbA1c) [units: Percentage of glycosylated hemoglobin] Least Squares Mean ± Standard Error	-1.00 ± 0.05	-1.14 ± 0.05

Statistical Analysis 1 for Change in Glycosylated Hemoglobin (HbA1c)

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	Mixed effect model repeat measures(MMRM)
P Value ^[4]	0.055
Mean Difference (Net) ^[5]	0.14
95% Confidence Interval	( -0.003 to 0.291 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The hypothesis was tested hierarchically that 1) exenatide BID is non-inferior to insulin aspart 70/30 BID for glycemic control (change in HbA1c, outcome measure 1), and 2) superior regarding the incidence of hypoglycemia (outcome measure 2). This is the first part of the hierarchical test.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	The planned sample size of 366 patients treated with metformin only (assuming 25% dropouts) gave a power of 85% to detect non-inferiority of exenatide BID for change in HbA1c (non-inferiority margin 0.4%; assumed common standard deviation of 1.1%).
[3]	Other relevant information, such as adjustments or degrees of freedom:
	95% CI of treatment group difference derived from MMRM (treatment, week, baseline HbA1c and interactions as fixed effects); p-value: superiority test
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Non-inferiority: upper limit of 95% Confidence Interval (CI) to be < 0.4%.
[5]	Other relevant estimation information:
	No text entered.

2. Primary:

Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode) [ Time Frame: 26 weeks ]

Measure Type	Primary
Measure Title	Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)
Measure Description	Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26
Time Frame	26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode) [units: Percentage of participants]	8.0	20.5

Statistical Analysis 1 for Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)

Groups ^[1]	All groups
Method ^[2]	Kaplan-Meier analysis
P Value ^[3]	<0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The hypothesis was tested hierarchically that 1) exenatide BID is non-inferior to insulin aspart BID for glycemic control (outcome measure 1), and 2) superior regarding the incidence of hypoglycemia (outcome measure 2).The planned sample size of 366 patients treated with metformin only (assumed dropout rate 25%) gave 96% power to detect superiority of exenatide BID for the risk of hypoglycemia, assuming incidences of 3.6% for exenatide BID and 17.5% for insulin aspart BID (alpha=0.05).
[2]	Other relevant information, such as adjustments or degrees of freedom:
	For each treatment group, the incidence of hypoglycemia at Week 26 and 95% CIs were derived from Kaplan-Meier analysis.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Non overlapping 95% CI's: statistically significant difference p<0.05.

3. Secondary:

Percentage of Subjects Achieving HbA1c Target of < 6.5% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Title	Percentage of Subjects Achieving HbA1c Target of < 6.5%
Measure Description	Percentage of subjects achieving HbA1c target of < 6.5% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 6.5% divided by total number of subjects times 100%].
Time Frame	26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Percentage of Subjects Achieving HbA1c Target of < 6.5% [units: Percentage of participants]	27.6	24.9

Statistical Analysis 1 for Percentage of Subjects Achieving HbA1c Target of < 6.5%

Groups ^[1]	All groups
Method ^[2]	Chi square test (Pearson)
P Value ^[3]	0.554

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

4. Secondary:

Percentage of Subjects Achieving HbA1c Target of < 7.0% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Title	Percentage of Subjects Achieving HbA1c Target of < 7.0%
Measure Description	Percentage of subjects achieving HbA1c target of < 7.0% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 7.0% divided by total number of subjects times 100%].
Time Frame	26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Percentage of Subjects Achieving HbA1c Target of < 7.0% [units: Percentage of participants]	49.2	56.6

Statistical Analysis 1 for Percentage of Subjects Achieving HbA1c Target of < 7.0%

Groups ^[1]	All groups
Method ^[2]	Chi square test (Pearson)
P Value ^[3]	0.159

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

5. Secondary:

Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period) [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Title	Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)
Measure Description	Risk for the first hypoglycemic episode to occur up to Week 26 (percentage of subjects who experienced at least one treatment-emergent hypoglycemic episode during the 26-week treatment period)[ i.e., number of subjects experiencing at least one hypoglycemic episode divided by total number of subjects times 100%]
Time Frame	26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period) [units: Percentage of participants]	1.8	6.3

No statistical analysis provided for Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)

6. Secondary:

Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period) [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Title	Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)
Measure Description	Risk for first nocturnal (night-time) hypoglycemic episode to occur up to week 26 (percentage of subjects who experienced at least one episode of nocturnal hypoglycemia during the 26 week treatment period) [i.e., number of subjects who experienced nocturnal hypoglycemia divided by total number of subjects times 100%].
Time Frame	26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period) [units: Percentage of participants]	3.9	7.0

No statistical analysis provided for Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)

7. Secondary:

7 Point Self-monitored Blood Glucose (SMBG) Profiles [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	7 Point Self-monitored Blood Glucose (SMBG) Profiles
Measure Description	7-point self-monitored blood glucose profiles at baseline and the end of the study, measured at 7 times during the day (pre-breakfast, 2 hours post-breakfast, pre-lunch, 2 hours post-lunch, pre-dinner, 2 hours post-dinner, and 3:00am).
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
7 Point Self-monitored Blood Glucose (SMBG) Profiles [units: mg/dL] Mean ± Standard Deviation
Pre-breakfast at baseline (week 0)	8.933 ± 1.7138	9.005 ± 2.0432
Pre-breakfast at endpoint (week 26)	7.774 ± 1.7730	7.293 ± 1.3349
2 hrs post-breakfast at baseline (week 0)	10.821 ± 2.5306	10.902 ± 2.8499
2 hrs post-breakfast at endpoint (week 26)	8.014 ± 2.0557	8.304 ± 2.1212
Pre-lunch at baseline (week 0)	8.443 ± 2.1814	8.357 ± 2.3221
Pre-lunch at endpoint (week 26)	7.506 ± 1.8800	6.656 ± 1.7011
2 hrs post-lunch at baseline (week 0)	9.698 ± 2.2370	9.899 ± 2.6433
2 hrs post-lunch at endpoint (week 26)	8.513 ± 5.8997	8.216 ± 1.6108
Pre-dinner at baseline (week 0)	8.684 ± 2.0059	8.759 ± 2.2174
Pre-dinner at endpoint (week 26)	7.616 ± 2.1727	7.194 ± 1.5572
2 hrs post-dinner at baseline (week 0)	10.241 ± 2.2880	10.259 ± 2.4868
2 hrs post-dinner at endpoint (week 26)	7.727 ± 1.8820	8.143 ± 1.5614
3:00 am at baseline (week 0)	8.323 ± 1.8692	8.475 ± 2.2643
3:00 am at endpoint (week 26)	7.518 ± 1.5861	6.999 ± 1.5596

No statistical analysis provided for 7 Point Self-monitored Blood Glucose (SMBG) Profiles

8. Secondary:

Blood Lipid Levels [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	Blood Lipid Levels
Measure Description	Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), and triglyceride levels at baseline (week 0) and the end of the study (week 26)
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Blood Lipid Levels [units: mmol/L] Mean ± Standard Deviation
Total cholesterol at baseline (week 0)	5.147 ± 1.0008	5.084 ± 1.0079
Total cholesterol at endpoint (week 26)	4.971 ± 0.9653	5.050 ± 0.8933
HDL cholesterol at baseline (week 0)	1.234 ± 0.3065	1.255 ± 0.3324
HDL cholesterol at endpoint (week 26)	1.244 ± 0.2805	1.319 ± 0.3394
LDL cholesterol (calculated) at baseline (week 0)	2.845 ± 0.8308	2.768 ± 0.8103
LDL cholesterol (calculated) at endpoint (week 26)	2.738 ± 0.8472	2.852 ± 0.8134
Triglycerides at baseline (week 0)	2.391 ± 1.5497	2.410 ± 1.4398
Triglycerides at endpoint (week 26)	2.234 ± 1.1886	2.006 ± 1.2040

No statistical analysis provided for Blood Lipid Levels

9. Secondary:

Change in Body Weight [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	Change in Body Weight
Measure Description	Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS) and had baseline and at least one post-baseline value available; last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Change in Body Weight [units: kg] Least Squares Mean ± Standard Error	-4.10 ± 0.22	1.02 ± 0.22

Statistical Analysis 1 for Change in Body Weight

Groups ^[1]	All groups
Method ^[2]	Mixed effects model repeated measures
P Value ^[3]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	95% CI of treatment group difference derived from MMRM (treatment, week, baseline HbA1c and interactions as fixed effects)
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The MMRM model adjusted for baseline HbA1c stratum (HbA1c at baseline >= 6.5% and <= 8.0% vs. > 8.0% and <=10%).

10. Secondary:

Change in Body Mass Index (BMI) [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	Change in Body Mass Index (BMI)
Measure Description	Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS) and had baseline and at least one post-baseline value available; last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Change in Body Mass Index (BMI) [units: kg/m^2] Least Squares Mean ± Standard Error	-1.39 ± 0.07	0.32 ± 0.07

Statistical Analysis 1 for Change in Body Mass Index (BMI)

Groups ^[1]	All groups
Method ^[2]	Mixed effects model repeated measures
P Value ^[3]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	95% CI of treatment group difference derived from MMRM (treatment, week, baseline HbA1c and interactions as fixed effects)
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The MMRM model adjusted for baseline HbA1c stratum (HbA1c at Visit 1 >= 6.5% and <= 8.0% vs. > 8.0% and <=10%).

11. Secondary:

Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ) [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)
Measure Description	Total DTSQ treatment satisfaction score at baseline (week 0) and after 26 weeks of treatment (LOCF). Total DTSQ treatment satisfaction score is derived as sum score of the individual components 1 and 4-8 of the DTSQ questionnaire. Each component is scored on a scale of 0 (worst case) to 6 (best case). Higher values represent higher treatment satisfaction.
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ) [units: scores on DTSQ scale] Mean ± Standard Deviation
DTSQ score at baseline (week 0)	29.5 ± 6.13	29.7 ± 6.25
DTSQ score at endpoint (week 26)	30.6 ± 6.05	29.3 ± 6.59

No statistical analysis provided for Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)

12. Secondary:

Patient Reported Outcomes: Quality of Life (SF-12) [ Time Frame: Baseline and 26 weeks ]

Measure Type	Secondary
Measure Title	Patient Reported Outcomes: Quality of Life (SF-12)
Measure Description	SF-12 Physical and Mental Component Summary Scores at baseline (week 0) and after 26 weeks of treatment (LOCF). SF-12 Physical and Mental Component Summary Scores are normalized scores ranging from 0 (worst case) to 100 (best case), and are derived from responses to 12 questions. Scores > 50 indicate an above-average health status.
Time Frame	Baseline and 26 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS); last observation carried forward

Reporting Groups

	Description
Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
Premixed Insulin Aspart Twice Daily	Premixed insulin aspart (70% protamin crystallized, 30% soluble) twice daily, individually titrated to reach target blood glucose levels for 26 weeks

Measured Values

	Exenatide Twice Daily	Premixed Insulin Aspart Twice Daily
Number of Participants Analyzed [units: participants]	181	173
Patient Reported Outcomes: Quality of Life (SF-12) [units: scores on SF-12 scale] Mean ± Standard Deviation
Physical Component at baseline (week 0)	35.5 ± 13.99	36.3 ± 14.45
Physical Component at endpoint (week 26)	39.1 ± 14.30	37.7 ± 14.28
Mental Component at baseline (week 0)	31.3 ± 18.33	28.3 ± 19.43
Mental Component at endpoint (week 26)	31.1 ± 19.38	29.6 ± 18.36

No statistical analysis provided for Patient Reported Outcomes: Quality of Life (SF-12)

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
e-mail: clinicaltrials@amylin.com

No publications provided by Amylin Pharmaceuticals, LLC.

Publications automatically indexed to this study:

Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.

Gallwitz B, Böhmer M, Segiet T, Mölle A, Milek K, Becker B, Helsberg K, Petto H, Peters N, Bachmann O. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011 Mar;34(3):604-6. Epub 2011 Feb 1.

Responsible Party:	Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:	NCT00434954 History of Changes
Other Study ID Numbers:	H8O-SB-GWBN
Study First Received:	February 12, 2007
Results First Received:	June 25, 2010
Last Updated:	February 11, 2013
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

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