Effect of Exenatide Plus Metformin vs. Insulin Aspart Plu... | NCT00434954

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
Exenatide Twice Daily (BID)	Experimental		Drug: exenatide twice daily (BID)
Premixed Insulin Aspart Twice Daily (BID)	Active Comparator		Drug: premixed insulin aspart twice daily (BID)

Name	Type	Description	Arm Group Labels	Other Names
exenatide twice daily (BID)	Drug	subcutaneous injection (5 mcg or 10 mcg), twice a day	Exenatide Twice Daily (BID)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)	Baseline and 26 weeks
Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)	Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26	26 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Subjects Achieving HbA1c Target of < 6.5%	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%].	26 weeks
Percentage of Subjects Achieving HbA1c Target of < 7.0%

Eligibility Module

Name	Affiliation	Role
Chief Medical Officer, MD	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Bad Mergentheim			Germany
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22913891	Derived	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.
21285388	Derived	Gallwitz B, Bohmer M, Segiet T, Molle 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. doi: 10.2337/dc10-1900. Epub 2011 Feb 1.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
FG001	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00057.2± 10.03 BG00156.9± 9.94 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00073 BG00177 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg / m^2

Title

Denominators

Categories

Title	Measurements
	BG00033.4± 4.23 BG00132.9± 4.37 BG002

Body Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00099.4± 16.22 BG00196.6± 17.40 BG002

Duration of Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0004.8± 4.39 BG0015.2± 4.67 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG0007.89± 0.822 BG0017.88± 0.918 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Glycosylated Hemoglobin (HbA1c)

Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)

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

Posted

Least Squares Mean

Standard Error

Percentage of glycosylated hemoglobin

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000181 OG001173

Title

Denominators

Categories

Title	Measurements
	OG000-1.00± 0.05 OG001-1.14± 0.05

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Mixed effect model repeat measures(MMRM)	95% CI of treatment group difference derived from MMRM (treatment, week, baseline HbA1c and interactions as fixed effects); p-value: superiority test	0.055	Non-inferiority: upper limit of 95% Confidence Interval (CI) to be < 0.4%.	Mean Difference (Net)	0.14			2-Sided	95	-0.003	0.291				Yes

Secondary

Percentage of Subjects Achieving HbA1c Target of < 6.5%

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%].

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

Posted

Number

Percentage of participants

26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Secondary

Percentage of Subjects Achieving HbA1c Target of < 7.0%

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%].

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

Posted

Number

Percentage of participants

26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

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)

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%]

All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Posted

Number

Percentage of participants

26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants

Secondary

Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)

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%].

All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Posted

Number

Percentage of participants

26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants

Secondary

7 Point Self-monitored Blood Glucose (SMBG) Profiles

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).

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

Posted

Mean

Standard Deviation

mg/dL

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Secondary

Blood Lipid Levels

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)

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

Posted

Mean

Standard Deviation

mmol/L

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Primary

Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)

Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26

All randomized patients who were previously treated with metformin only and who received at least one dose of study drug (MET only, FAS)

Posted

Number

Percentage of participants

26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Secondary

Change in Body Weight

Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)

Posted

Least Squares Mean

Standard Error

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Secondary

Change in Body Mass Index (BMI)

Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)

Posted

Least Squares Mean

Standard Error

kg/m^2

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants	OG000

Secondary

Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)

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.

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

Posted

Mean

Standard Deviation

scores on DTSQ scale

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants

Secondary

Patient Reported Outcomes: Quality of Life (SF-12)

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.

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

Posted

Mean

Standard Deviation

scores on SF-12 scale

Baseline and 26 weeks

ID	Title	Description
OG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
OG001	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

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Angina pectoris	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Breast abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Bronchopneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Coronary artery disease	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0011 affected233 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0011 affected233 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0002 affected247 at risk EG0010 affected233 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Hepatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Nerve injury	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Parkinson's disease	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected247 at risk EG0011 affected233 at risk
Syncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 affected247 at risk EG0010 affected233 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00027 affected247 at risk EG00116 affected233 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00026 affected247 at risk EG00125 affected233 at risk
Nasopharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00037 affected247 at risk EG00142 affected233 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00046 affected247 at risk EG0018 affected233 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00022 affected247 at risk EG0012 affected233 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00015 affected247 at risk EG0012 affected233 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D014688	Venoms
D045424	Complex Mixtures
D014118	Toxins, Biological
D001685	Biological Factors

ID	Title	Description
BG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks
BG001	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
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Exenatide Twice Daily	Exenatide 5 mcg twice daily for 4 weeks, followed by 10 mcg twice daily for 26 weeks			9	247	102	247
EG001	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			8	233	66	233