Exenatide Versus Glimepiride in Patients With Type 2 Diab... | NCT00359762

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Exenatide	Experimental		Drug: exenatide
Glimepiride	Active Comparator		Drug: glimepiride

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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With Treatment Failure	Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.	Baseline to end of Period II (up to 4.5 years)
Time to Treatment Failure	Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.	Baseline to end of Period II (up to 4.5 years)

Secondary Outcomes

Measure	Description	Time Frame
Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3	HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175).	Year 3 in Period II
Change in HOMA-B From Baseline to Endpoint

Eligibility Module

Name	Affiliation	Role
James Malone, MD	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Graz			Austria
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26338040	Derived	Simo R, Guerci B, Schernthaner G, Gallwitz B, Rosas-Guzman J, Dotta F, Festa A, Zhou M, Kiljanski J. Long-term changes in cardiovascular risk markers during administration of exenatide twice daily or glimepiride: results from the European exenatide study. Cardiovasc Diabetol. 2015 Sep 4;14:116. doi: 10.1186/s12933-015-0279-z.
25846577

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Period II, Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
FG001	Period III, Exen + Met + Glim - Randomized

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
BG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
BG002	Total	Total of all reporting groups

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
	BG00056.1± 10.03 BG00156.8± 9.14 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000218 BG001235 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

percentage of total hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0007.4± 0.69 BG0017.4± 0.71 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00092.8± 16.70 BG00191.1± 14.78 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

Number of Patients With Treatment Failure

Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.

ITT Efficacy Population: Enrolled patients with a baseline and at least one post-baseline measurement of HbA1c in Study Period II (including only Study Period II); patients analyzed according to treatment as randomized.

Posted

Number

number of patients

Baseline to end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000490 OG001487

Title

Denominators

Categories

Number of patients with treatment failure

Title	Measurements
	OG000203 OG001262

Number of patients censored

Title	Measurements
	OG000

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 null hypothesis (H0) and alternative hypothesis (H1) for the primary analysis (i.e., non-inferiority) are:H0: hazards of treatment for Exenatide/hazards of treatment for Glimepiride >=1.25.H1: hazards of treatment for Exenatide/hazards of treatment for Glimepiride < 1.25. With 527 patients in each arm, the study would have approximately 90% power to conclude non-inferiority of Exenatide to Glimepiride.	Regression, Cox	Time to treatment failure was modeled using Cox regression with treatment and baseline HbA1c as predictive terms.	0.0020		Hazard Ratio	0.748			2-Sided	95	0.623	0.899				Yes

Primary

Time to Treatment Failure

ITT Efficacy Population.

Posted

Median

95% Confidence Interval

week

Baseline to end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3

HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175).

ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

ratio

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Change in HOMA-B From Baseline to Endpoint

Change in HOMA-B from baseline to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Fasting Proinsulin/Insulin Ratio at Year 3

Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3.

Posted

Least Squares Mean

Standard Error

ratio

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.

Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3

DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin - fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose - fasting glucose) (measured in mmol/L).

Posted

Least Squares Mean

Standard Error

ratio

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Change in DI30/DG30 Ratio From Baseline to Endpoint

Change in DI30/DG30 ratio from baseline to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Disposition Index at Year 3

Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175).

Posted

Least Squares Mean

Standard Error

ratio

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Change in Disposition Index From Baseline to Endpoint

Change in disposition index from baseline to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in HbA1c From Baseline to Year 3

Change in HbA1c from baseline to Year 3.

Posted

Least Squares Mean

Standard Error

percentage of total hemoglobin

Baseline, Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in HbA1c From Baseline to Endpoint

Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study).

ITT Efficacy Population.

Posted

Least Squares Mean

Standard Error

percentage of total hemoglobin

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Fasting Plasma Glucose at Year 3

Fasting plasma glucose at Year 3.

Posted

Least Squares Mean

Standard Error

mmol/L

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in Fasting Plasma Glucose From Baseline to Endpoint

Change in fasting plasma glucose from baseline to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Postprandial (2 Hours) Plasma Glucose at Year 3

Postprandial (2 hours) plasma glucose at Year 3.

Posted

Least Squares Mean

Standard Error

mmol/L

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint

Change from baseline in postprandial (2 hours) plasma glucose to endpoint.

ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Change in Body Weight From Baseline to Year 3

Change in Body weight from baseline to Year 3.

ITT Safety Population: Enrolled patients receiving at least one dose of study medication in Study Period II with patients analyzed according to treatment actually received. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

Baseline, Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants

Secondary

Systolic Blood Pressure at Year 3

Systolic Blood pressure at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

mmHg

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Diastolic Blood Pressure at Year 3

Diastolic Blood pressure at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

mmHg

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Heart Rate at Year 3

Heart rate at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

beats per minute

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Triglycerides at Year 3

Triglycerides at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

mmol/L

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Total Cholesterol at Year 3

Total Cholesterol at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

mmol/L

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

High-density Lipoprotein (HDL) Cholesterol at Year 3

HDL Cholesterol at Year 3.

ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.

Posted

Least Squares Mean

Standard Error

mmol/L

Year 3 in Period II

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts
Participants	OG000

Secondary

Hypoglycemia Rate Per Year

All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.

ITT Safety Population.

Posted

Least Squares Mean

Standard Error

events per subject-year

Baseline to end of Period II (up to 4.5 years)

ID	Title	Description
OG000	Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
OG001	Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin

Units	Counts

Secondary

Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III

Change in HbA1c from baseline to Year 2.

Extension ITT Efficacy Population: Extension enrolled patients with at least one post-baseline measurement of HbA1c in Study Period III. The analysis included patients randomized at entry in study period III. Missing data at Year 2 was not imputed.

Posted

Least Squares Mean

Standard Error

percentage of total hemoglobin

Baseline in Period III, Year 2 in Period III

ID	Title	Description
OG000	Exen + Met + Glim - Randomized	Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
OG001	Exen + Met + Pio or Rosi - Randomized	Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III

Units	Counts
Participants

Secondary

Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III

Change in HbA1c from baseline to Year 2.

Extension ITT Efficacy population. The analysis included patients not randomized at entry in study period III. Missing data at Year 2 was not imputed.

Posted

Mean

Standard Deviation

percentage of total hemoglobin

Baseline in Period III, Year 2 in Period III

ID	Title	Description
OG000	Glim + Met + Exen - Not Randomized	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III

Units	Counts
Participants	OG000

Secondary

Hypoglycemia Rate Per Year in Period III

Extension ITT Safety Population: Extension enrolled patients receiving at least one dose of study medication in Study Period III.

Posted

Mean

Standard Deviation

events per subject-year

Start of Period III to end of study

ID	Title	Description
OG000	Exen + Metformin + Glim - Randomized	Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
OG001	Exen + Met + Pio or Rosi - Randomized	Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
OG002

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Period II, Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin	68	508	248	508
EG001	Period III, Exen + Met + Glim - Randomized	Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III	7	74	39	74
EG002	Period III, Exen + Met + Pio or Rosi - Randomized	Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III	13	76	39	76
EG003	Period III, Glim + Met + Exen - Not Randomized	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III	19	166	91	166
EG004	Period II, Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin	73	511	311	511

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG0031 affected166 at risk EG004
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Erysipelas	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Syncope	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Tachyarrhythmia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Abscess	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Abscess limb	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Brain contusion	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Bullous lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Carotid arteriosclerosis	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cellulitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Colonic polyp	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Encephalitis	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Gallbladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
HIV infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Haemophilia A with anti factor VIII	Congenital, familial and genetic disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Helicobacter gastritis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Influenza	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Injury	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Palpitations	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pubis fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Radiculopathy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sciatica	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sinusitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sternal fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sudden cardiac death	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0003 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Uterine cervical erosion	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Viral labyrinthitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Abdominal adhesions	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Accident	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Acute abdomen	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Anal abscess	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Angle closure glaucoma	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Appendicitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0002 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Calculus ureteric	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Cardiac disorder	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Carpal tunnel syndrome	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Chondropathy	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Dermoid cyst	Congenital, familial and genetic disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Endometrial hypertrophy	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Gastric neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Goitre	Endocrine disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0011 affected74 at risk EG0020 affected76 at risk EG003
Infected epidermal cyst	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Intervertebral discitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Knee deformity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Localised infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Macular oedema	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0004 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Mental disorder	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Mood altered	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Nervous system disorder	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Rectosigmoid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Renal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected508 at risk EG0010 affected74 at risk EG0021 affected76 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Sports injury	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Staphylococcal sepsis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Transient global amnesia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Ureteric injury	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Urinary bladder polyp	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Urinary tract inflammation	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected508 at risk EG0010 affected74 at risk EG0020 affected76 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00011 affected508 at risk EG00110 affected74 at risk EG0029 affected76 at risk EG00338 affected166 at risk EG004147 affected511 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00093 affected508 at risk EG00120 affected74 at risk EG00215 affected76 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00033 affected508 at risk EG0017 affected74 at risk EG0027 affected76 at risk EG003
Headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG00048 affected508 at risk EG00111 affected74 at risk EG0027 affected76 at risk EG003
Influenza	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00035 affected508 at risk EG0017 affected74 at risk EG0026 affected76 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG00054 affected508 at risk EG0015 affected74 at risk EG0029 affected76 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00012 affected508 at risk EG0014 affected74 at risk EG0021 affected76 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00031 affected508 at risk EG0012 affected74 at risk EG0027 affected76 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00014 affected508 at risk EG0014 affected74 at risk EG0020 affected76 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00021 affected508 at risk EG0012 affected74 at risk EG0022 affected76 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00013 affected508 at risk EG0016 affected74 at risk EG0022 affected76 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG00041 affected508 at risk EG0012 affected74 at risk EG0022 affected76 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00025 affected508 at risk EG0014 affected74 at risk EG0024 affected76 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00013 affected508 at risk EG0014 affected74 at risk EG0023 affected76 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG00022 affected508 at risk EG0013 affected74 at risk EG0022 affected76 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG00024 affected508 at risk EG0016 affected74 at risk EG0023 affected76 at risk EG003
Cystitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG00019 affected508 at risk EG0015 affected74 at risk EG0023 affected76 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00010 affected508 at risk EG0014 affected74 at risk EG0021 affected76 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.1	Non-systematic Assessment	EG00011 affected508 at risk EG0010 affected74 at risk EG0025 affected76 at risk EG003

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