Safety and Efficacy of Exenatide Once Weekly Injection Ve... | NCT00676338

NCT00676338

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Exenatide Once Weekly	Experimental	Drug: exenatide once weekly
Metformin	Active Comparator	Drug: metformin
Sitagliptin	Active Comparator	Drug: sitagliptin
Pioglitazone	Active Comparator	Drug: pioglitazone

Name	Type	Description	Arm Group Labels	Other Names
exenatide once weekly	Drug	subcutaneous injection, 2mg, once weekly plus placebo oral once daily	Exenatide Once Weekly

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c From Baseline to Week 26	Change in HbA1c from baseline to Week 26.	Baseline, Week 26
Percentage of Patients Achieving HbA1c <=7% at Week 26	Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%).	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change in Fasting Serum Glucose (FSG) From Baseline to Week 26	Change in FSG from baseline to Week 26.	Baseline, Week 26
Change in Body Weight From Baseline to Week 26	Change in Body Weight from baseline to Week 26.

Eligibility Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Buena Park	California		United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32306296	Derived	Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.
23748507	Derived	Malloy J, Meloni A, Han J. Efficacy and tolerability of exenatide once weekly versus sitagliptin in patients with type 2 diabetes mellitus: a retrospective analysis of pooled clinical trial data. Postgrad Med. 2013 May;125(3):58-67. doi: 10.3810/pgm.2013.05.2661.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
FG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
BG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
BG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
BG003	Sitagliptin	Sitagliptin (100 mg/day for 26 weeks) + weekly subcutaneous placebo injection
BG004	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 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00053.7± 10.91 BG00153.7± 11.08 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000109 BG00192 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

percentage of total hemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.5± 1.19 BG0018.6± 1.20 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00087.5± 18.88 BG00185.9± 19.57 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 HbA1c From Baseline to Week 26

Change in HbA1c from baseline to Week 26.

Intent to treat (ITT) population consisted of all randomized patients who had taken at least one dose of study drug. All scheduled post-baseline measurements were included in the analysis. Unscheduled visit observations were carried forward to the next scheduled visits.

Posted

Least Squares Mean

Standard Error

percentage of total hemoglobin

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin	Sitagliptin (100 mg/day for 26 weeks) + weekly subcutaneous placebo injection

Units	Counts
Participants	OG000218 OG001218 OG002137 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.53± 0.07 OG001-1.48± 0.07 OG002-1.63± 0.08 OG003

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	Power calculation: A sample of 740 (222 exenatide once weekly, 222 metformin, 148 pioglitazone, and 148 sitagliptin) would provide approximately 90% power to detect a true differences between exenatide once weekly and the 3 comparators: metformin, pioglitazone, and sitagliptin of 0.4%, 0.5%, and 0.5%, respectively in change in HbA1c from baseline to Week 26 with a 2-sided t test at a significance level of 0.05, assuming a common standard deviation of 1.2%.	Mixed Models Analysis		0.620	Noninferiority was tested by Bonferroni (margin 0.3%, adjusted significance of 0.0167). Superiority was tested by Hommel (nominal significance level was between 0.0167 and 0.05 depended on the number of noninferiority hypotheses rejected).	Least Squares Mean Difference	-0.05	Standard Error of the Mean	0.09	2-Sided	98.3	-0.26	0.17

Primary

Percentage of Patients Achieving HbA1c <=7% at Week 26

Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%).

ITT subjects with baseline HbA1c>7%. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.

Posted

Number

percentage of patients

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Change in Fasting Serum Glucose (FSG) From Baseline to Week 26

Change in FSG from baseline to Week 26.

ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Change in Body Weight From Baseline to Week 26

Change in Body Weight from baseline to Week 26.

Posted

Least Squares Mean

Standard Error

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Change in Fasting Total Cholesterol (TC) From Baseline to Week 26

Change in Fasting TC from baseline to Week 26.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26

Change in Fasting HDL from baseline to Week 26.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Ratio of Fasting Triglycerides at Week 26 to Baseline

Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline.

ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using LOCF approach.

Posted

Least Squares Mean

Standard Error

ratio

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events

Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).

ITT population.

Posted

Mean

Standard Error

events per subject-year

Baseline to Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone

Secondary

Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events

Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).

ITT population.

Posted

Mean

Standard Error

events per subject-year

Baseline to Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection

Secondary

Change in Systolic Blood Pressure From Baseline to Week 26.

Change in Systolic Blood Pressure from baseline to Week 26.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Secondary

Change in Diastolic Blood Pressure From Baseline to Week 26.

Change in Diastolic Blood Pressure from baseline to Week 26.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline, Week 26

ID	Title	Description
OG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo
OG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection
OG003	Sitagliptin

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Exenatide Once Weekly	Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo	4	248	109	248
EG001	Metformin	Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection	12	246	94	246
EG002	Pioglitazone	Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection	9	163	57	163
EG003	Sitagliptin	Sitagliptin (100 mg/day for 26 weeks) + weekly subcutaneous placebo injection	3	163	55	163

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Calculus ureteric	Renal and urinary disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG0030 affected163 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Joint sprain	Injury, poisoning and procedural complications	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 13.0	Non-systematic Assessment	EG0001 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Arteriovenous malformation	Congenital, familial and genetic disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Arteritis	Vascular disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Bronchopneumopathy	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Cardiopulmonary failure	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Cellulitis	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Chest pain	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Chondromalacia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Diabetic foot	Metabolism and nutrition disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Hepatic neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Hysterectomy	Surgical and medical procedures	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Lumbar hernia	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Oedema	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Peritonsillar abscess	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0020 affected163 at risk EG003
Typhoid fever	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG0020 affected163 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003
Wound infection	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0010 affected246 at risk EG0021 affected163 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00028 affected248 at risk EG00117 affected246 at risk EG0026 affected163 at risk EG0036 affected163 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00027 affected248 at risk EG00131 affected246 at risk EG0026 affected163 at risk EG003
Injection site nodule	General disorders	MedDRA 13.0	Non-systematic Assessment	EG00026 affected248 at risk EG00125 affected246 at risk EG0026 affected163 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00021 affected248 at risk EG0018 affected246 at risk EG0023 affected163 at risk EG003
Headache	Nervous system disorders	MedDRA 13.0	Non-systematic Assessment	EG00020 affected248 at risk EG00130 affected246 at risk EG00213 affected163 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Non-systematic Assessment	EG00019 affected248 at risk EG00111 affected246 at risk EG00214 affected163 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 13.0	Non-systematic Assessment	EG00018 affected248 at risk EG0018 affected246 at risk EG0028 affected163 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG00013 affected248 at risk EG0013 affected246 at risk EG0025 affected163 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Non-systematic Assessment	EG0006 affected248 at risk EG00114 affected246 at risk EG0027 affected163 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.0	Non-systematic Assessment	EG0003 affected248 at risk EG0013 affected246 at risk EG00212 affected163 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.0	Non-systematic Assessment	EG0000 affected248 at risk EG0011 affected246 at risk EG00212 affected163 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines
D045162	Thiazolidinediones
D013844	Thiazoles
D013457	Sulfur Compounds

ID	Term
D008687	Metformin
D000068900	Sitagliptin Phosphate
D000077205	Pioglitazone