A Study to Evaluate the Efficacy and Safety of MEDI0382 i... | NCT03235050

Status Module

Name	Class
MedImmune LLC	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MEDI0382 low dose + Metformin	Experimental	Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Drug: MEDI0382 low dose
MEDI0382 mid dose + Metformin	Experimental	Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Drug: MEDI0382 mid dose
MEDI0382 high dose + Metformin	Experimental	Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Drug: MEDI0382 high dose
Placebo + Metformin	Placebo Comparator	Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Drug: Placebo
Liraglutide + Metformin	Active Comparator	Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	Drug: Liraglutide

Name	Type	Description	Arm Group Labels	Other Names
MEDI0382 low dose	Drug	Pharmaceutical form: solution Route of administration: subcutaneous	MEDI0382 low dose + Metformin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c	To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo	From baseline to 14 weeks
Percent Change in Body Weight	To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo	From baseline to 14 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change in HbA1c	To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo	from baseline to 26 weeks and 54 weeks
Percentage of Participants Achieving an HbA1c Target < 7.0%

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of informed consent
Male and female subjects aged ≥ 18 years at screening
Body mass index ≥ 25 kg/m2 at screening
HbA1c range of 7.0% to 10.5% (inclusive) at screening
Diagnosed with type-2 diabetes mellitus (T2DM) and treated with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 2 months prior to screening. Use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening is acceptable
Women of childbearing potential (WOCBP), not breastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product (IP), with a negative pregnancy test within 72 hours prior to the start of IP

Exclusion Criteria:

History of, or any existing condition that, in the opinion of the Investigator, would interfere with evaluation of the IP, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
Any subject who has received another IP as part of a clinical study or a GLP-1 receptor agonist containing preparation within the last 30 days or 5 half lives of the drug (whichever is longer) at the time of screening
Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
Symptoms of acutely decompensated blood glucose control, a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily subcutaneous (SC) insulin for a period longer than 2 weeks within 90 days prior to screening
Acute or chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening
Significant inflammatory bowel disease or other severe disease or surgery affecting the upper Gastrointestinal (GI) tract
Significant hepatic disease
Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤30 mL/minute/1.73m2 at screening
Severely uncontrolled hypertension
Unstable angina pectoris, myocardial infarction (MI), transient ischaemic attack (TIA), or stroke within 3 months prior to screening
Severe congestive heart failure

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama	35205	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
34016612	Derived	Nahra R, Wang T, Gadde KM, Oscarsson J, Stumvoll M, Jermutus L, Hirshberg B, Ambery P. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care. 2021 Jun;44(6):1433-1442. doi: 10.2337/dc20-2151. Epub 2021 May 20.

Label	URL
D5670C00004 SAP redacted	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
FG001	Liraglutide	Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 4, 2018	Jul 31, 2020

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
BG001	Liraglutide	Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
BG002	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
BG003	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
BG004	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
BG005	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, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00057.3± 9.5 BG00155.5± 9.8 BG00257.6± 9.9 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00055 BG00160 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0003 BG0013 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

To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

ITT population

Posted

Least Squares Mean

95% Confidence Interval

percentage

From baseline to 14 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Units	Counts
Participants	OG000112 OG001100 OG002256 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.18(-0.34 to -0.02) OG001-1.01(-1.18 to -0.84) OG002-1.22(-1.33 to -1.11) 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		ANCOVA		<0.001		LS Mean Difference	-0.83			2-Sided	95	-1.06	-0.59					Superiority
OG000 OG002		ANCOVA		<0.001

Primary

Percent Change in Body Weight

To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

ITT population

Posted

Least Squares Mean

95% Confidence Interval

percentage

From baseline to 14 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Change in HbA1c

To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

ITT population

Posted

Least Squares Mean

95% Confidence Interval

percentage

from baseline to 26 weeks and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Percentage of Participants Achieving an HbA1c Target < 7.0%

To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo

Intent-to-Treat (ITT) population

Posted

Count of Participants

Participants

after 14, 26, and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Percent Change in Body Weight

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo

ITT population

Posted

Least Squares Mean

95% Confidence Interval

percentage

from baseline to 26 weeks and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Absolute Change in Body Weight

To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

ITT population

Posted

Least Squares Mean

95% Confidence Interval

from baseline to 14 weeks, 26 weeks and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Percent Change in Body Weight Versus Active Comparator

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

ITT population

Posted

Least Squares Mean

95% Confidence Interval

percentage

from baseline to 14 weeks, 26 weeks and 54 weeks

ID	Title	Description
OG000	Liraglutide	Liraglutide / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Absolute Change in Body Weight Versus Active Comparator

To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

ITT population

Posted

Least Squares Mean

95% Confidence Interval

from baseline to 14 weeks, 26 weeks and 54 weeks

ID	Title	Description
OG000	Liraglutide	Liraglutide / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Percentage of Participants Achieving Weight Loss of ≥5% and ≥10%

To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo

ITT population

Posted

Count of Participants

Participants

after 14 weeks, 26 weeks and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control

To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo

ITT population

Posted

Count of Participants

Participants

at 14 weeks, 26 weeks and 54 weeks

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)

To characterise the PK profile of 100, 200, and 300 μg of cotadutide

Per-protocol population

Posted

Mean

Standard Deviation

ng/mL

Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)

To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

As-treated population

Posted

Count of Participants

Participants

Baseline through 54-week treatment period and 28-day follow-up

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Secondary

Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants

To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

As-treated population

Posted

Median

Full Range

titer

Baseline through 54-week treatment period and 28-day follow-up

ID	Title	Description
OG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG001	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG002	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
OG003	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	0	112	12	112	45	112
EG001	Liraglutide	Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	0	110	8	110	36	110
EG002	MEDI0382 100 mcg	MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	0	100	12	100	51	100
EG003	MEDI0382 200 mcg	MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	2	256	33	256	159	256
EG004	MEDI0382 300 mcg	MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)	1	256	20	256	164	256

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG0031 events1 affected256 at risk EG0040 events0 affected256 at risk
Angina pectoris	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Aortic valve stenosis	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0022 events1 affected100 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Silent myocardial infarction	Cardiac disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Retinal detachment	Eye disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Retinal tear	Eye disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Enterocutaneous fistula	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Gastric polyps	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Megacolon	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Retroperitoneal haematoma	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Impaired healing	General disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Gallbladder polyp	Hepatobiliary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Acarodermatitis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Appendicitis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Bacterial infection	Infections and infestations	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Cellulitis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Chronic sinusitis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Erysipelas	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Otitis media acute	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0022 events2 affected100 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Pyelonephritis chronic	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Skin infection	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Anastomotic leak	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Arterial bypass occlusion	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Post procedural fistula	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Spinal column injury	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Subcutaneous haematoma	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Arthrofibrosis	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Haematoma muscle	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Meniscal degeneration	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Acute leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Gastrointestinal stromal tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Tongue neoplasm malignant stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Triple negative breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Cerebrovascular disorder	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003
Diabetic neuropathy	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Vertigo cns origin	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Perinephritis	Renal and urinary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Prerenal failure	Renal and urinary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Urinary tract disorder	Renal and urinary disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Acquired phimosis	Reproductive system and breast disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0011 events1 affected110 at risk EG0020 events0 affected100 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Vocal cord dysfunction	Respiratory, thoracic and mediastinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Hypertension	Vascular disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0020 events0 affected100 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0021 events1 affected100 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0002 events2 affected112 at risk EG0013 events2 affected110 at risk EG0021 events1 affected100 at risk EG00310 events10 affected256 at risk EG00414 events13 affected256 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG00010 events10 affected112 at risk EG0017 events4 affected110 at risk EG00215 events13 affected100 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0002 events2 affected112 at risk EG0013 events3 affected110 at risk EG00213 events7 affected100 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0000 events0 affected112 at risk EG0010 events0 affected110 at risk EG0022 events2 affected100 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG00013 events12 affected112 at risk EG00121 events17 affected110 at risk EG00228 events23 affected100 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22	Systematic Assessment	EG0006 events5 affected112 at risk EG0013 events3 affected110 at risk EG00212 events10 affected100 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22	Systematic Assessment	EG00019 events15 affected112 at risk EG00113 events11 affected110 at risk EG00213 events11 affected100 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA 22	Systematic Assessment	EG0003 events3 affected112 at risk EG0011 events1 affected110 at risk EG0021 events1 affected100 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22	Systematic Assessment	EG0006 events6 affected112 at risk EG0012 events2 affected110 at risk EG0024 events3 affected100 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0011 events1 affected110 at risk EG0023 events3 affected100 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22	Systematic Assessment	EG0006 events6 affected112 at risk EG0012 events2 affected110 at risk EG0028 events8 affected100 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0003 events3 affected112 at risk EG0010 events0 affected110 at risk EG0025 events4 affected100 at risk EG003
Headache	Nervous system disorders	MedDRA 22	Systematic Assessment	EG0001 events1 affected112 at risk EG0015 events5 affected110 at risk EG0024 events3 affected100 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
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists