Effect on Weight Loss of Exenatide Versus Placebo - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Condition:	Type 2 Diabetes Mellitus
Interventions:	Drug: exenatide Drug: placebo

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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	Group A (Exenatide)	Group B (Placebo)
STARTED	96	98
COMPLETED	70	72
NOT COMPLETED	26	26
Adverse Event	4	5
Entry Criteria Not Met	0	1
Loss of Glucose Control	0	1
Lost to Follow-up	10	5
Physician Decision	0	4
Protocol Violation	6	3
Sponsor Decision	0	1
Subject Decision	6	6

	Group A (Exenatide)	Group B (Placebo)	Total
Number of Participants [units: participants]	96	98	194
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	78	82	160
>=65 years	18	16	34
Age [units: years] Mean ± Standard Deviation	54.52 ± 10.02	55.08 ± 8.97	54.81 ± 9.48
Gender [units: participants]
Female	60	61	121
Male	36	37	73
Baseline Body Weight [units: kg] Mean ± Standard Deviation	94.90 ± 16.52	96.16 ± 16.53	95.53 ± 16.05
Baseline Cholesterol [units: mmol/L] Mean ± Standard Deviation	4.67 ± 1.03	4.68 ± 0.90	4.68 ± 0.96
Baseline Glycosylated Hemoglobin (HbA1c) [units: %] Mean ± Standard Deviation	7.74 ± 0.87	7.51 ± 0.82	7.62 ± 0.85
Baseline High Density Lipoprotein (HDL) Cholesterol [units: mmol/L] Mean ± Standard Deviation	1.18 ± 0.32	1.21 ± 0.31	1.20 ± 0.31
Baseline Homeostatic Model Assessment-Beta Cell (HOMA-B) [units: %] Mean ± Standard Deviation	75.15 ± 81.20	70.72 ± 53.16	72.81 ± 67.65
Baseline Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) [units: %] Mean ± Standard Deviation	49.72 ± 32.12	62.90 ± 41.07	56.68 ± 37.57
Baseline Low Density Lipoprotein (LDL) Cholesterol [units: mmol/L] Mean ± Standard Deviation	2.74 ± 0.88	2.78 ± 0.82	2.76 ± 0.85
Baseline Triglycerides [units: mmol/L] Mean ± Standard Deviation	2.15 ± 0.94	2.13 ± 1.00	2.14 ± 0.97
Baseline Waist Circumference [units: cm] Mean ± Standard Deviation	109.64 ± 11.12	108.85 ± 12.10	109.24 ± 11.60

Measure Type	Primary
Measure Title	Change in Body Weight
Measure Description	Change in body weight from baseline after 24 weeks of treatment (i.e., weight at week 24 minus weight at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	70	72
Change in Body Weight [units: kg] Least Squares Mean ± Standard Error
Change in body weight at week 24	-6.16 ± 0.54	-3.97 ± 0.52

Statistical Analysis 1 for Change in Body Weight

Groups ^[1]	All groups
Method ^[2]	Mixed Model Repeated Measures
P Value ^[3]	0.0030

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
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[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.

Measure Type	Secondary
Measure Title	Change in Glycosylated Hemoglobin (HbA1c)
Measure Description	Change in HbA1c from baseline after 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	70	71
Change in Glycosylated Hemoglobin (HbA1c) [units: %] Least Squares Mean ± Standard Error
Change in HbA1c at week 24	-1.21 ± 0.09	-0.73 ± 0.09

Statistical Analysis 1 for Change in Glycosylated Hemoglobin (HbA1c)

Groups ^[1]	All groups
Method ^[2]	Mixed Model Repeated Measures
P Value ^[3]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
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[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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Measure Type	Secondary
Measure Title	Change in 6-point Self Monitored Blood Glucose (SMBG) Profile.
Measure Description	Change in SMBG at each of 6 time points throughout a day (blood glucose measurements before and 2 hours after the start of the morning, mid-day, and evening meals); week 24 compared to week 0 (i.e., SMBG at week 24 minus SMBG at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	69	72
Change in 6-point Self Monitored Blood Glucose (SMBG) Profile. [units: mmol/L] Least Squares Mean ± Standard Error
Morning Pre-Meal	-1.87 ± 0.17	-1.20 ± 0.17
2 Hours Post Morning Meal	-2.67 ± 0.22	-1.92 ± 0.22
Midday Pre-Meal	-1.40 ± 0.19	-1.37 ± 0.19
2 Hours Post Midday Meal	-2.12 ± 0.21	-1.51 ± 0.20
Evening Pre-Meal	-1.57 ± 0.19	-1.32 ± 0.19
2 Hours Post Evening Meal	-3.09 ± 0.22	-2.28 ± 0.23

No statistical analysis provided for Change in 6-point Self Monitored Blood Glucose (SMBG) Profile.

Measure Type	Secondary
Measure Title	Change in Waist Circumference.
Measure Description	Change in waist circumference from baseline after 24 weeks of treatment (i.e., waist circumference at week 24 minus waist circumference at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	69	69
Change in Waist Circumference. [units: cm] Least Squares Mean ± Standard Error
Change in waist circumference at week 24	-5.33 ± 0.71	-4.18 ± 0.73

Statistical Analysis 1 for Change in Waist Circumference.

Groups ^[1]	All groups
Method ^[2]	Mixed Model Repeated Measures
P Value ^[3]	0.1985

[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.

Measure Type	Secondary
Measure Title	Change in Homeostatic Model Assessment-Beta Cell (HOMA-B)
Measure Description	Ratio of HOMA-B at week 24 to HOMA-B at week 0 (i.e., HOMA-B at week 24 divided by HOMA-B at week 0). HOMA-B is a measure of beta cell function.
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	68	76
Change in Homeostatic Model Assessment-Beta Cell (HOMA-B) [units: Ratio] Geometric Mean ± Standard Error
Ratio (HOMA-B at wk 24 / HOMA-B at wk 0)	1.46 ± 0.12	1.29 ± 0.10

Statistical Analysis 1 for Change in Homeostatic Model Assessment-Beta Cell (HOMA-B)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.1827

[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.

Measure Type	Secondary
Measure Title	Change in Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S)
Measure Description	Ratio of HOMA-S at week 24 to HOMA-S at week 0 (i.e., HOMA-S at week 24 divided by HOMA-S at week 0). HOMA-S is a measure of insulin sensitivity.
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	68	76
Change in Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) [units: Ratio] Geometric Mean ± Standard Error
Ratio (HOMA-S at wk 24 / HOMA-S at wk 0)	1.08 ± 0.07	0.97 ± 0.06

Statistical Analysis 1 for Change in Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.1584

[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.

Measure Type	Secondary
Measure Title	Change in High Density Lipoprotein (HDL) Cholesterol
Measure Description	Change in HDL cholesterol from baseline after 24 weeks of treatment (i.e., HDL cholesterol at week 24 minus HDL cholesterol at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	81	89
Change in High Density Lipoprotein (HDL) Cholesterol [units: mmol/L] Least Squares Mean ± Standard Error
Change in HDL Cholesterol at week 24	0.02 ± 0.02	0.02 ± 0.02

Statistical Analysis 1 for Change in High Density Lipoprotein (HDL) Cholesterol

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.8279

[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.

Measure Type	Secondary
Measure Title	Change in Low Density Lipoprotein (LDL) Cholesterol
Measure Description	Change in LDL cholesterol from baseline after 24 weeks of treatment (i.e., LDL cholesterol at week 24 minus LDL cholesterol at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	81	89
Change in Low Density Lipoprotein (LDL) Cholesterol [units: mmol/L] Least Squares Mean ± Standard Error
Change in LDL cholesterol at week 24	-0.06 ± 0.08	-0.04 ± 0.07

Statistical Analysis 1 for Change in Low Density Lipoprotein (LDL) Cholesterol

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.8334

[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.

Measure Type	Secondary
Measure Title	Change in Total Cholesterol
Measure Description	Change in total cholesterol from baseline after 24 weeks of treatment (i.e., total cholesterol at week 24 minus total cholesterol at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	81	89
Change in Total Cholesterol [units: mmol/L] Least Squares Mean ± Standard Error
Change in total cholesterol at week 24	-0.16 ± 0.10	-0.03 ± 0.10

Statistical Analysis 1 for Change in Total Cholesterol

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.2881

[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.

Measure Type	Secondary
Measure Title	Change in Triglycerides
Measure Description	Ratio of triglyceride levels at week 24 to triglyceride levels at week 0 (i.e., triglycerides at week 24 divided by triglycerides at week 0)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	81	89
Change in Triglycerides [units: Ratio] Geometric Mean ± Standard Error
Ratio (triglycerides wk 24 / triglycerides wk 0)	0.83 ± 0.04	0.92 ± 0.04

Statistical Analysis 1 for Change in Triglycerides

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.0654

[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.

Measure Type	Secondary
Measure Title	Incidence of Hypoglycemic Events
Measure Description	Number of patients experiencing one or more events of hypoglycemia at any point in the study
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	96	98
Incidence of Hypoglycemic Events [units: participants]
Number of participants experiencing hypoglycemia	33	30

Statistical Analysis 1 for Incidence of Hypoglycemic Events

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.728

[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.

Measure Type	Secondary
Measure Title	Rate of Hypoglycemic Events
Measure Description	Overall rate of hypoglycemia, adjusted for 1 year (i.e., events of hypoglycemia per patient per year)
Time Frame	24 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.
Intent to Treat population

Reporting Groups

	Description
Group A (Exenatide)	exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 20 weeks
Group B (Placebo)	placebo (volume equivalent to exenatide injection) twice daily for 24 weeks

Measured Values

	Group A (Exenatide)	Group B (Placebo)
Number of Participants Analyzed [units: participants]	96	98
Rate of Hypoglycemic Events [units: events per patient per year] Least Squares Mean ± Standard Error
Rate (hypoglycemic events per patient per year)	7.14 ± 1.45	4.58 ± 1.43

Statistical Analysis 1 for Rate of Hypoglycemic Events

Groups ^[1]	All groups
Method ^[2]	ANOVA
P Value ^[3]	0.127

[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.

Responsible Party:	Eli Lilly and Company ( James Malone, MD, Study Director )
Study ID Numbers:	H8O-US-GWBM
Study First Received:	September 11, 2006
Results First Received:	February 25, 2009
Last Updated:	July 30, 2009
ClinicalTrials.gov Identifier:	NCT00375492 History of Changes
Health Authority:	United States: Food and Drug Administration